Integrity of the corpus callosum in patients with periventricular nodular heterotopia related epilepsy by FLNA mutation.

PubMed

Liu, Wenyu; An, Dongmei; Niu, Running; Gong, Qiyong; Zhou, Dong

2018-01-01

To investigate the quantitative diffusion properties of the corpus callosum (CC) in a large group of patients with periventricular nodular heterotopia (PNH) related epilepsy and to further investigate the effect of Filamin A ( FLNA ) mutation on these properties. Patients with PNH (n = 34), subdivided into FLNA -mutated (n = 11) and FLNA -nonmutated patients (n = 23) and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion imaging scan (64 direction). Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the three major subdivisions of the CC (genu, body and splenium). Correlations between DTI metric changes and clinical parameters were also evaluated. Furthermore, the effect of FLNA mutation on structural integrity of the corpus callosum was examined. Patients with PNH and epilepsy had significant reductions in FA for the genu and splenium of the CC, accompanied by increases in MD for the splenium, as compared to healthy controls. There were no correlations between clinical parameters of epilepsy and MD. The FA value in the splenium negatively correlated with epilepsy duration. Interestingly, FLNA -mutated patients showed significantly decreased FA for all three major subdivisions of the CC, and increased MD for the genu and splenium, as compared to HCs and FLNA -nonmutated patients. These findings support the conclusion that patients with epilepsy secondary to PNH present widespread microstructural changes found in the corpus callosum that extend beyond the macroscopic MRI-visible lesions. This study also indicates that FLNA may affect white matter integrity in this disorder.

Boomerang sign on MRI.

PubMed

Hirsch, Karen G; Hoesch, Robert E

2012-06-01

Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients. Case report with relevant image and review of the literature. Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology. Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

Visual interhemispheric communication and callosal connections of the occipital lobes.

PubMed

Berlucchi, Giovanni

2014-07-01

Callosal connections of the occipital lobes, coursing in the splenium of the corpus callosum, have long been thought to be crucial for interactions between the cerebral hemispheres in vision in both experimental animals and humans. Yet the callosal connections of the temporal and parietal lobes appear to have more important roles than those of the occipital callosal connections in at least some high-order interhemispheric visual functions. The partial intermixing and overlap of temporal, parietal and occipital callosal connections within the splenium has made it difficult to attribute the effects of splenial pathological lesions or experimental sections to splenial components specifically related to select cortical areas. The present review describes some current contributions from the modern techniques for the tracking of commissural fibers within the living human brain to the tentative assignation of specific visual functions to specific callosal tracts, either occipital or extraoccipital. Copyright © 2013 Elsevier Ltd. All rights reserved.

Left hand tactile agnosia after posterior callosal lesion.

PubMed

Balsamo, Maddalena; Trojano, Luigi; Giamundo, Arcangelo; Grossi, Dario

2008-09-01

We report a patient with a hemorrhagic lesion encroaching upon the posterior third of the corpus callosum but sparing the splenium. She showed marked difficulties in recognizing objects and shapes perceived through her left hand, while she could appreciate elementary sensorial features of items tactually presented to the same hand flawlessly. This picture, corresponding to classical descriptions of unilateral associative tactile agnosia, was associated with finger agnosia of the left hand. This very unusual case report can be interpreted as an instance of disconnection syndrome, and allows a discussion of mechanisms involved in tactile object recognition.

Dichotic listening in patients with splenial and nonsplenial callosal lesions.

PubMed

Pollmann, Stefan; Maertens, Marianne; von Cramon, D Yves; Lepsien, Joeran; Hugdahl, Kenneth

2002-01-01

The authors found splenial lesions to be associated with left ear suppression in dichotic listening of consonant-vowel syllables. This was found in both a rapid presentation dichotic monitoring task and a standard dichotic listening task, ruling out attentional limitations in the processing of high stimulus loads as a confounding factor. Moreover, directed attention to the left ear did not improve left ear target detection in the patients, independent of callosal lesion location. The authors' data may indicate that auditory callosal fibers pass through the splenium more posterior than previously thought. However, further studies should investigate whether callosal fibers between primary and secondary auditory cortices, or between higher level multimodal cortices, are vital for the detection of left ear targets in dichotic listening.

Splenium microstructure is related to two dimensions of reading skill.

PubMed

Frye, Richard E; Hasan, Khader; Xue, Lian; Strickland, David; Malmberg, Benjamin; Liederman, Jacqueline; Papanicolaou, Andrew

2008-10-29

Inconsistent differences in the corpus callosum (CC) structure between dyslexic readers (DRs) and typical readers (TRs) have been reported. We examine differences in CC splenium microstructure and the association of splenium microstructure with reading-related skills. Nine DRs and 18 TRs completed a reading skills battery and diffusion tensor imaging. DRs had higher splenium fractional anisotropy (FA) and axial diffusivity (LA) as compared with TRs. Retrieval of orthographic information from the language lexicon was negatively associated with FA and LA within both reading groups. Phonological awareness was positively associated with splenium FA and LA in TRs but not DRs. This study suggests two white matter pathways that may be differentially associated with reading skills in the CC splenium.

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

PubMed

Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

2016-03-01

Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

Regional Microstructural and Volumetric Magnetic Resonance Imaging (MRI) Abnormalities in the Corpus Callosum of Neonates With Congenital Heart Defect Undergoing Cardiac Surgery.

PubMed

Hagmann, Cornelia; Singer, Jitka; Latal, Beatrice; Knirsch, Walter; Makki, Malek

2016-03-01

The purpose of the study is to investigate the structural development of the corpus callosum in term neonates with congenital heart defect before and after surgery using diffusion tensor imaging and 3-dimensional T1-weighted magnetic resonance imaging (MRI). We compared parallel and radial diffusions, apparent diffusion coefficient (ADC), fractional anisotropy, and volume of 5 substructures of the corpus callosum: genu, rostral body, body, isthmus, and splenium. Compared to healthy controls, we found a significantly lower volume of the splenium and total corpus callosum and a higher radial diffusion and lower fractional anisotropy in the splenium of patients presurgery; a lower volume in all substructures in the postsurgery group; higher radial diffusion in the rostral body, body, and splenium; and a higher apparent diffusion coefficient in the splenium of postsurgery patients. Similar fractional anisotropy changes in congenital heart defect patients were reported in preterm infants. Our findings in apparent diffusion coefficient in the splenium of these patients (pre and postsurgery) are comparable to findings in preterm neonates with psychomotor delay. Delayed maturation of the isthmus was also reported in preterm infants. © The Author(s) 2015.

Importance of correctly interpreting magnetic resonance imaging to diagnose posterior reversible encephalopathy syndrome associated with HELLP syndrome: a case report.

PubMed

Tetsuka, Syuichi; Nonaka, Hiroaki

2017-05-25

Severe haemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome in pregnancy are possible underlying trigger factors for posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) shows diffuse signal abnormalities involving the subcortical white matter in the parieto-occipital lobes. Although the diagnosis of RPES was clearly established by the distinctive reversibility of clinical and radiological abnormalities, it is difficult to distinguish from differential diagnosis. Thus, it is important to correctly interpret MRI. We describe a case of HELLP syndrome with PRES. A 38-year-old pregnant woman was admitted to our hospital as an emergency case with a complaint of upper abdominal pain and headache at 29 weeks of pregnancy and the development of HELLP syndrome. An emergency caesarean section was immediately performed. After the operation, the patient received intravenous corticosteroids, and her blood pressure was controlled. Thereafter, she showed an altered mental status. MRI showed hypersignal intense lesions in the cortical and subcortical white matter in the occipital lobes, basal ganglia and callosal splenium in both the fluid-attenuated inversion recovery (FLAIR) sequence and apparent diffusion coefficient (ADC), but these lesions were not recognized in diffusion-weighted imaging (DWI). These images were suggestive of PRES. The patient was kept in the hospital and received the appropriate treatment, after which the patient's level of consciousness improved and all laboratory tests and imaging examinations returned normal. The MRI findings were useful for the prompt diagnosis of PRES, characterized by hypersignals in FLAIR and ADC, but not in DWI. Additionally, there was an "atypical" MRI appearance of basal ganglial and callosal splenial involvement in this case, which may mistakenly lead clinicians to diagnose other aetiologies than typical PRES. It is considered that vasogenic oedema is the main pathology of PRES according to the MRI image findings. MRI is the gold standard for diagnosing PRES because it can provide information about cerebral involvement earlier than CT; further, it can be a useful tool in the differential diagnosis. This technique facilitated the prompt diagnosis and treatment of the said patient, ultimately resulting in a good outcome.

Splenium of Corpus Callosum: Patterns of Interhemispheric Interaction in Children and Adults

PubMed Central

Knyazeva, Maria G.

2013-01-01

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain. PMID:23577273

Right unilateral agraphia following callosal infarction in a left-hander.

PubMed

Tei, H; Soma, Y; Maruyama, S

1994-01-01

A left-handed Japanese man is reported who presented right-hand agraphia and tactile anomia following callosal infarction. Magnetic resonance imaging revealed an ischemic lesion extending from the posterior half of the trunk to the splenium of the corpus callosum. In his right handwriting, the 'Kana' (phonogram) was more severely impaired than the 'Kanji' (ideogram), and the most frequent typewriting error was morphological followed by neographism. His visuoconstructional ability was also more impaired in the right hand than in the left. Right-hand agraphia in our case is readily explained by the right hemisphere dominance both for language and visuoconstructional ability.

A stimulus-centered reading disorder for words and numbers: Is it neglect dyslexia?

PubMed

Arduino, Lisa S; Daini, Roberta; Caterina Silveri, Maria

2005-12-01

A single case, RCG, showing a unilateral reading disorder without unilateral spatial neglect was studied. The disorder was characterized by substitutions of the initial (left) letters of words, nonwords and Arabic numbers, independently of egocentered spatial coordinates. MRI showed a bilateral lesion with the involvement of the splenium. Although, within the framework of the visual word recognition model proposed by Caramazza and Hillis (1990), RCG disorder could be defined as a stimulus-centered neglect dyslexia, we discuss the hypothesis of a dissociation in neural correlates and mechanisms between the syndrome of unilateral spatial neglect and such a unilateral reading disorder.

White matter lesional predictors of chronic visual neglect: a longitudinal study

PubMed Central

Lunven, Marine; Thiebaut De Schotten, Michel; Bourlon, Clémence; Duret, Christophe; Migliaccio, Raffaella; Rode, Gilles

2015-01-01

Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient’s lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect. PMID:25609686

Splenium Development and Early Spoken Language in Human Infants

ERIC Educational Resources Information Center

Swanson, Meghan R.; Wolff, Jason J.; Elison, Jed T.; Gu, Hongbin; Hazlett, Heather C.; Botteron, Kelly; Styner, Martin; Paterson, Sarah; Gerig, Guido; Constantino, John; Dager, Stephen; Estes, Annette; Vachet, Clement; Piven, Joseph

2017-01-01

The association between developmental trajectories of language-related white matter fiber pathways from 6 to 24 months of age and individual differences in language production at 24 months of age was investigated. The splenium of the corpus callosum, a fiber pathway projecting through the posterior hub of the default mode network to occipital…

Sustained diffusion reversal with in-bore reperfusion in monkey stroke models: Confirmed by prospective magnetic resonance imaging

PubMed Central

Yi, Kyung Sik; Choi, Chi-Hoon; Lee, Sang-Rae; Lee, Hong Jun; Lee, Youngjeon; Jeong, Kang-Jin; Hwang, Jinwoo; Chang, Kyu-Tae

2016-01-01

Although early diffusion lesion reversal after recanalization treatment of acute ischaemic stroke has been observed in clinical settings, the reversibility of lesions observed by diffusion-weighted imaging remains controversial. Here, we present consistent observations of sustained diffusion lesion reversal after transient middle cerebral artery occlusion in a monkey stroke model. Seven rhesus macaques were subjected to endovascular transient middle cerebral artery occlusion with in-bore reperfusion confirmed by repeated prospective diffusion-weighted imaging. Early diffusion lesion reversal was defined as lesion reversal at 3 h after reperfusion. Sustained diffusion lesion reversal was defined as the difference between the ADC-derived pre-reperfusion maximal ischemic lesion volume (ADCD-P Match) and the lesion on 4-week follow-up FLAIR magnetic resonance imaging. Diffusion lesions were spatiotemporally assessed using a 3-D voxel-based quantitative technique. The ADCD-P Match was 9.7 ± 6.0% (mean ± SD) and the final infarct was 1.2–6.0% of the volume of the ipsilateral hemisphere. Early diffusion lesion reversal and sustained diffusion lesion reversal were observed in all seven animals, and the calculated percentages compared with their ADCD-P Match ranged from 8.3 to 51.9% (mean ± SD, 26.9 ± 15.3%) and 41.7–77.8% (mean ± SD, 65.4 ± 12.2%), respectively. Substantial sustained diffusion lesion reversal and early reversal were observed in all animals in this monkey model of transient focal cerebral ischaemia. PMID:27401804

Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children.

PubMed

Rose, Jessica; Butler, Erin E; Lamont, Lauren E; Barnes, Patrick D; Atlas, Scott W; Stevenson, David K

2009-07-01

The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term-equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel-Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very-low-birthweight preterm children (41 males, 37 females; mean gestational age 27.6 wks, SD 2.5; mean birthweight 1021 g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.

Abnormal brain MRI signals in the splenium of the corpus callosum, basal ganglia and internal capsule in a suspected case with tuberculous meningitis.

PubMed

Hirotani, Makoto; Yabe, Ichiro; Hamada, Shinsuke; Tsuji, Sachiko; Kikuchi, Seiji; Sasaki, Hidenao

2007-01-01

A 34-year-old man visited the hospital with chief complaints of headache, fever, and disturbance of consciousness. In view of his clinical condition, the course of the disease, and results of examination, he was diagnosed with viral meningitis and treated accordingly. However, his clinical condition worsened, and MRI revealed abnormal signals in the splenium of the corpus callosum, in the basal ganglia and in the internal capsule, as well as the presence of severe inflammation in the base of the brain. Since he had a high ADA level in the cerebrospinal fluid and was consequently suspected to have tuberculous meningitis, he was placed on antitubercular agents. Then, his clinical condition began to improve. Additional steroid pulse therapy further improved his condition, and abnormal signals in the splenium of the corpus callosum and the basal ganglia resolved. This valuable case suggests that an immune mechanism contributed to the occurrence of central nervous system symptoms associated with tuberculous meningitis.

Intracranial imaging of uncommon diseases is more frequently reported in clinical publications than in radiology publications.

PubMed

Lehman, V T; Doolittle, D A; Hunt, C H; Eckel, L J; Black, D F; Schwartz, K M; Diehn, F E

2014-01-01

Descriptions of uncommon diseases with intracranial imaging abnormalities are often difficult to find in the radiology literature. We hypothesized that reported imaging findings of such conditions in the recent literature were more frequent in clinical compared with radiology journals. PubMed searches from December 1, 2007 to December 1, 2012 were performed for 5 uncommon CNS diseases with intracranial imaging manifestations: 1) Susac syndrome; 2) amyloid β-related angiitis; 3) Parry-Romberg syndrome/en coup de sabre; 4) transient lesion of the splenium of the corpus callosum; and 5) reversible cerebral vasoconstriction syndrome. Articles were classified as a case report, case series, or original research. Journals were categorized as radiology or clinical. The 1- and 5-year Impact Factors of the journals were recorded. Two hundred two articles were identified for the 5 diseases, including 151 (74%) case reports, 26 case series (13%), and 25 original research articles (13%); 179 (89%) were published in nonradiology journals, compared with 23 (11%) in radiology journals. There was no significant difference between the mean 1- and 5-year Impact Factors of the radiology and clinical journals. Recent reports of the selected uncommon diseases with intracranial manifestations are more frequent in clinical journals when compared with dedicated radiology publications. Most publications are case reports. Radiologists should review both radiology and clinical journals when reviewing imaging features of uncommon diseases affecting the brain. Lack of reporting on such disease in the radiology literature may have significant practice, educational, and research implications for the radiology community.

Step-by-Step Technique for Segmental Reconstruction of Reverse Hill-Sachs Lesions Using Homologous Osteochondral Allograft.

PubMed

Alkaduhimi, Hassanin; van den Bekerom, Michel P J; van Deurzen, Derek F P

2017-06-01

Posterior shoulder dislocations are accompanied by high forces and can result in an anteromedial humeral head impression fracture called a reverse Hill-Sachs lesion. This reverse Hill-Sachs lesion can result in serious complications including posttraumatic osteoarthritis, posterior dislocations, osteonecrosis, persistent joint stiffness, and loss of shoulder function. Treatment is challenging and depends on the amount of bone loss. Several techniques have been reported to describe the surgical treatment of lesions larger than 20%. However, there is still limited evidence with regard to the optimal procedure. Favorable results have been reported by performing segmental reconstruction of the reverse Hill-Sachs lesion with bone allograft. Although the procedure of segmental reconstruction has been used in several studies, its technique has not yet been well described in detail. In this report we propose a step-by-step description of the technique how to perform a segmental reconstruction of a reverse Hill-Sachs defect.

Neural connectivity of the posterior body of the fornix in the human brain: diffusion tensor imaging study.

PubMed

Jang, Sung Ho; Kwon, Hyeok Gyu

2013-08-09

Little is known about the neural connectivity of the fornix in the human brain. In the current study, using diffusion tensor imaging, we attempted to investigate the neural connectivity of the posterior body of the fornix in the normal human brain. A total of 43 healthy subjects were recruited for this study. DTIs were acquired using a sensitivity-encoding head coil at 1.5T. For connectivity of the posterior body of the fornix, a seed region of interest was used on the posterior body of the fornix. Connectivity was defined as the incidence of connection between the posterior body of the fornix and any neural structure of the brain at the threshold of 5, 25, and 50 streamline. At the threshold of 5, 25, and 50, the posterior body of the fornix showed connectivity to the precentral gyrus (37%, 19%, and 15%), the postcentral gyrus (25%, 11.5%, and 7%), the posterior parietal cortex (16.5%, 5%, and 5%), the brainstem (12%, 4.5%, and 3.5%), the crus of the fornix (34%, 10.5%, and 7%), the contralateral splenium of the corpus callosum (12.5%, 5%, and 0%), and the ipsilateral splenium of the CC (69.8%%, 33.7%, and 23.3%), respectively. Findings of this study showed that the posterior body of the fornix had connectivity with the cerebral cortex, the brainstem, the fornical crus, and the contralateral splenium through the splenium of the corpus callosum in normal subjects. We believe that the results of this study would be helpful in investigation of the neural network related to memory and recovery mechanisms following fornical injury in the human brain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mapping callosal morphology in early- and late-onset elderly depression: an index of distinct changes in cortical connectivity.

PubMed

Ballmaier, Martina; Kumar, Anand; Elderkin-Thompson, Virginia; Narr, Katherine L; Luders, Eileen; Thompson, Paul M; Hojatkashani, Cornelius; Pham, Daniel; Heinz, Andreas; Toga, Arthur W

2008-06-01

There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age = 68.00, SD+/-5.83), 22 patients with late-onset depression (mean age = 74.50, SD+/-8.09) and 34 elderly control subjects (mean age = 72.38; SD+/-6.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late- vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late- from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late- and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than early-onset depression, with potentially important implications for research and therapy.

Electron microscopic examination of the myelinated axons of corpus callosum in perfused young and old rats.

PubMed

Sargon, Mustafa F; Denk, C Cem; Celik, H Hamdi; Surucu, H Selcuk; Aldur, M Mustafa

2007-07-01

In this study, the myelinated axons of parts of the corpus callosums of young and old rats were examined under the electron microscope and a grading system was performed for quantitating the ultrastructural pathological changes of these axons. Except the old splenium group, the only ultrastructural pathological change, observed in the myelinated axons was the separation in myelin configuration. In addition to this finding, in the old splenium group, in some of the myelinated axons, an interruption was observed in the myelin configuration. Additionally, these ultrastructural pathological findings were present in the larger sized myelinated axons of the corpus callosum.

Magnetic resonance features of cerebral malaria.

PubMed

Yadav, P; Sharma, R; Kumar, S; Kumar, U

2008-06-01

Cerebral malaria is a major health hazard, with a high incidence of mortality. The disease is endemic in many developing countries, but with a greater increase in tourism, occasional cases may be detected in countries where the disease in not prevalent. Early diagnosis and evaluation of cerebral involvement in malaria utilizing modern imaging modalities have an impact on the treatment and clinical outcome. To evaluate the magnetic resonance (MR) features of patients with cerebral malaria presenting with altered sensorium. We present the findings in three patients with cerebral malaria presenting with altered sensorium. MR imaging using a 1.5-Tesla unit was carried out. The sequences performed were 5-mm-thick T1-weighted, T2-weighted, fluid-attenuated inversion-recovery (FLAIR), and T2-weighted gradient-echo axial sequences, and sagittal and coronal FLAIR. Diffusion-weighted imaging was performed with b values of 0 and 1000 s/mm(2), and apparent diffusion coefficient (ADC) maps were obtained. Focal hyperintensities in the bilateral periventricular white matter, corpus callosum, occipital subcortex, and bilateral thalami were noticed on T2-weighted and FLAIR sequences. The lesions were more marked in the splenium of the corpus callosum. No enhancement on postcontrast T1-weighted MR images was observed. There was no evidence of restricted diffusion on the diffusion-weighted sequence and ADC map. MR is a sensitive imaging modality, with a role in the assessment of cerebral lesions in malaria. Focal white matter and corpus callosal lesions without any restricted diffusion were the key findings in our patients.

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

PubMed

Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

2013-01-01

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

PubMed

Chudasama, Y; Robbins, Trevor W

2003-09-24

To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.

Reversible splenial lesion syndrome associated with lobar pneumonia

PubMed Central

Li, Chunrong; Wu, Xiujuan; Qi, Hehe; Cheng, Yanwei; Zhang, Bing; Zhou, Hongwei; Lv, Xiaohong; Liu, Kangding; Zhang, Hong-Liang

2016-01-01

Abstract Background: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological disorder with unclear pathophysiology. Clinically, RESLES is defined as reversible isolated splenial lesions in the corpus callosum, which can be readily identified by magnetic resonance imaging (MRI) and usually resolve completely over a period of time. RESLES could be typically triggered by infection, antiepileptic drugs (AEDs), poisoning, etc. More factors are increasingly recognized. Methods and results: We reported herein an 18-year-old female patient with lobar pneumonia who developed mental abnormalities during hospitalization. An isolated splenial lesion in the corpus callosum was found by head MRI and the lesion disappeared 15 days later. Based on her clinical manifestations and radiological findings, she was diagnosed with lobar pneumonia associated RESLES. We further summarize the up-to-date knowledge about the etiology, possible pathogenesis, clinical manifestations, radiological features, treatment, and prognosis of RESLES. Conclusion: This report contributes to the clinical understanding of RESLES which may present with mental abnormalities after infection. The characteristic imaging of reversible isolated splenial lesions in the corpus callosum was confirmed in this report. The clinical manifestations and lesions on MRI could disappear naturally after 1 month without special treatment. PMID:27684805

Effects of orbitofrontal cortex lesions on autoshaped lever pressing and reversal learning.

PubMed

Chang, Stephen E

2014-10-15

A cue associated with a rewarding event can trigger behavior towards the cue itself due to the cue acquiring incentive value through its pairing with the rewarding outcome (i.e., sign-tracking). For example, rats will approach, press, and attempt to "consume" a retractable lever conditioned stimulus (CS) that signals delivery of a food unconditioned stimulus (US). Attending to food-predictive CSs is important when seeking out food, and it is just as important to be able to modify one's behavior when the relationships between CSs and USs are changed. Using a discriminative autoshaping procedure with lever CSs, the present study investigated the effects of orbitofrontal cortex (OFC) lesions on sign-tracking and reversal learning. Insertion of one lever was followed by sucrose delivery upon retraction, and insertion of another lever was followed by nothing. After the acquisition phase, the contingencies between the levers and outcomes were reversed. Bilateral OFC lesions had no effect on the acquisition of sign-tracking. However, OFC-lesioned rats showed substantial deficits in acquiring sign-tracking compared to sham-lesioned rats once the stimulus-outcome contingencies were reversed. Over the course of reversal learning, OFC-lesioned rats were able to reach comparable levels of sign-tracking as sham-lesioned rats. These findings suggest that OFC is not necessary for the ability of a CS to acquire incentive value and provide more evidence that OFC is critical for modifying behavior appropriately following a change in stimulus-outcome contingencies. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevalence of neurologic lesions after total shoulder arthroplasty.

PubMed

Lädermann, A; Lübbeke, A; Mélis, B; Stern, R; Christofilopoulos, P; Bacle, G; Walch, G

2011-07-20

Clinically evident neurologic injury of the involved limb after total shoulder arthroplasty is not uncommon, but the subclinical prevalence is unknown. The purposes of this prospective study were to determine the subclinical prevalence of neurologic lesions after reverse shoulder arthroplasty and anatomic shoulder arthroplasty, and to evaluate the correlation of neurologic injury to postoperative lengthening of the arm. All patients undergoing either a reverse or an anatomic shoulder arthroplasty were included during the period studied. This study focused on the clinical, radiographic, and preoperative and postoperative electromyographic evaluation, with measurement of arm lengthening in patients who had reverse shoulder arthroplasty according to a previously validated protocol. Between November 2007 and February 2009, forty-one patients (forty-two shoulders) underwent reverse shoulder arthroplasty (nineteen shoulders) or anatomic primary shoulder arthroplasty (twenty-three shoulders). The two groups were similar with respect to sex distribution, preoperative neurologic lesions, and Constant score. Electromyography performed at a mean of 3.6 weeks postoperatively in the reverse shoulder arthroplasty group showed subclinical electromyographic changes in nine shoulders, involving mainly the axillary nerve; eight resolved in less than six months. In the anatomic shoulder arthroplasty group, a brachial plexus lesion was evident in one shoulder. The prevalence of acute postoperative nerve injury was significantly more frequent in the reverse shoulder arthroplasty group (p = 0.002), with a 10.9 times higher risk (95% confidence interval, 1.5 to 78.5). Mean lengthening (and standard deviation) of the arm after reverse shoulder arthroplasty was 2.7 ± 1.8 cm (range, 0 to 5.9 cm) compared with the normal, contralateral side. The occurrence of peripheral neurologic lesions following reverse shoulder arthroplasty is relatively common, but usually transient. Arm lengthening with a reverse shoulder arthroplasty may be responsible for these nerve injuries.

Reversible Hippocampal Lesions Disrupt Water Maze Performance during Both Recent and Remote Memory Tests

ERIC Educational Resources Information Center

Broadbent, Nicola J.; Squire, Larry R.; Clark, Robert E.

2006-01-01

Conventional lesion methods have shown that damage to the rodent hippocampus can impair previously acquired spatial memory in tasks such as the water maze. In contrast, work with reversible lesion methods using a different spatial task has found remote memory to be spared. To determine whether the finding of spared remote spatial memory depends on…

Lesions of the Medial Striatum in Monkeys Produce Perseverative Impairments during Reversal Learning Similar to Those Produced by Lesions of the Orbitofrontal Cortex

PubMed Central

Clarke, Hannah F.; Robbins, Trevor W.; Roberts, Angela C.

2014-01-01

The ability to switch responding between two visual stimuli based on their changing relationship with reward is dependent on the orbitofrontal cortex (OFC). OFC lesions in humans, monkeys, and rats disrupt performance on a common test of this ability, the visual serial discrimination reversal task. This finding is of particular significance to our understanding of psychiatric disorders such as obsessive–compulsive disorder (OCD) and schizophrenia, in which behavioral inflexibility is a prominent symptom. Although OFC dysfunction can occur in these disorders, there is considerable evidence for more widespread dysfunction within frontostriatal and frontoamygdalar circuitry. Because the contribution of these subcortical structures to behavioral flexibility is poorly understood, the present study compared the effects of excitotoxic lesions of the medial striatum (MS), amygdala, and OFC in the marmoset monkey on performance of the serial reversal task. All monkeys were able to learn a novel stimulus–reward association but, compared with both control and amygdala-lesioned monkeys, those with MS or OFC lesions showed a perseverative impairment in their ability to reverse this association. However, whereas both MS and OFC groups showed insensitivity to negative feedback, only OFC-lesioned monkeys showed insensitivity to positive feedback. These findings suggest that, for different reasons, both the MS and OFC support behavioral flexibility after changes in reward contingencies, and are consistent with the hypothesis that striatal and OFC dysfunction can contribute to pathological perseveration. PMID:18945905

The Neuropsychology of Ventral Prefrontal Cortex: Decision-Making and Reversal Learning

ERIC Educational Resources Information Center

Clark, L.; Cools, R.; Robbins, T. W.

2004-01-01

Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that…

Callosal involvement in a lateralized stroop task in alcoholic and healthy subjects.

PubMed

Schulte, T; Müller-Oehring, E M; Salo, R; Pfefferbaum, A; Sullivan, E V

2006-11-01

To investigate the role of interhemispheric attentional processes, 25 alcoholic and 28 control subjects were tested with a Stroop match-to-sample task and callosal areas were measured with magnetic resonance imaging. Stroop color-word stimuli were presented to the left or right visual field (VF) and were preceded by a color cue that did or did not match the word's color. For matching colors, both groups showed a right VF advantage; for nonmatching colors, controls showed a left VF advantage, whereas alcoholic subjects showed no VF advantage. For nonmatch trials, VF advantage correlated with callosal splenium area in controls but not alcoholic subjects, supporting the position that information presented to the nonpreferred hemisphere is transmitted via the splenium to the hemisphere specialized for efficient processing. The authors speculate that alcoholism-associated callosal thinning disrupts this processing route.

Posterior shoulder dislocation with a reverse Hill-Sachs lesion treated with frozen femoral head bone allograft combined with osteochondral autograft transfer.

PubMed

Mastrokalos, Dimitrios S; Panagopoulos, Georgios N; Galanopoulos, Ioannis P; Papagelopoulos, Panayiotis J

2017-10-01

Management of a posterior shoulder dislocation with an associated reverse Hill-Sachs lesion is challenging, both diagnostically and therapeutically. Diagnosis is frequently delayed or missed, whereas the resulting humeral head defect is often larger and more difficult to salvage than in anterior shoulder dislocations. This report presents the case of a 29-year-old male with a recurrent posterior shoulder dislocation associated with a large reverse Hill-Sachs defect, treated with bone augmentation of the lesion with a combination of fresh femoral head allograft and a locally harvested humeral head autograft transfer, with a successful outcome. Level of evidence V.

Elimination of the negative component of the unipolar atrial electrogram as an in vivo marker of transmural lesion creation: acute study in canines.

PubMed

Bortone, Agustín; Brault-Noble, Guillaume; Appetiti, Anthony; Marijon, Eloi

2015-08-01

It has been experimentally shown that elimination of the negative component of the unipolar atrial electrogram (R morphology completion) during radiofrequency applications reflects transmural lesions creation. Subsequently, it has been clinically suggested that such a transmurality can be either irreversible or reversible. The present study is aimed to determine, at the histological level, whether transmural lesions, assessed by R morphology completion, might indeed be reversible in some circumstances or not. In 6 Mongrel hound dogs, superior and inferior vena cavae were isolated and individual lesions were created in the right atrium using radiofrequency energy (30 W/48°C/17 mL/min as presettings and 10g of force in average) under CARTO guidance. Five types of lesions were created; R+0: termination of ablation at the time of R morphology completion; R+5, R+10, or R+20: extension of ablation for 5, 10, or 20 seconds, respectively, after R morphology achievement; and conventional: radiofrequency applications lasting 30 seconds irrespective of the atrial electrogram modification. All conventional, R+5, R+10, and R+20 lesions were necrotic and transmural, whereas some R+0 lesions were not (comprising a part of necrosis and a part of reversible cell damage). Interestingly, surrounding organ injuries were observed after conventional, R+10, and R+20 radiofrequency applications but were not observed after R+0 and R+5 applications. Elimination of the negative component of the unipolar atrial electrogram reflects, in general, irreversible transmural necrosis creation. In some cases, however, it translates transmural lesion only (with potential reversibility) likely related to transient cell damage creation. © 2015 American Heart Association, Inc.

Basolateral amygdala lesions and sensitivity to reinforcer magnitude in concurrent chains schedules.

PubMed

Helms, Christa M; Mitchell, Suzanne H

2008-08-22

Previous studies show that the basolateral amygdala (BLA) is required for behavior to adjust when the value of a reinforcer decreases after satiation or pairing with gastric distress. This study evaluated the effect of pre- or post-training excitotoxic lesions of the BLA on changes in preference with another type of contingency change, reinforcer magnitude reversal. Rats were trained to press left and right levers during a variable-interval choice phase for 50 microl or 150 microl sucrose delivered to consistent locations after a 16-s delay. Tones were presented during the first and last 2s of the delay to reinforcement. The tone frequency predicted the magnitude of sucrose reinforcement in baseline conditions. All groups acquired stable preference for the lever on the large (150 microl) reinforcer side. However, nose poking during the delay to large reinforcement was highly accurate (i.e., to the reinforced side) for all groups except the rats with BLA lesions induced before training, suggesting impaired control of behavior by the tone. After the acquisition of stable preference, the locations of the reinforcer magnitudes were unpredictably reversed for a single session. Pre-training lesions blunted changes in preference when the reinforcer magnitudes were reversed. Lesions induced after stable preference was acquired, but prior to reversal, did not disrupt changes in preference. The data suggest that the BLA contributes to the adaptation of choice behavior following changes in reinforcer magnitude. Impaired learning about the tone-reinforcer magnitude relationships may have disrupted discrimination of the reinforcer magnitude reversal.

Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting: Comparison of several anti-embolic protection devices.

PubMed

Taha, Mahmoud M; Maeda, Masayuki; Sakaida, Hiroshi; Kawaguchi, Kenji; Toma, Naoki; Yamamoto, Akitaka; Hirose, Tomofumi; Miura, Youichi; Fujimoto, Masashi; Matsushima, Satoshi; Taki, Waro

2009-09-01

Distal embolism is an important periprocedural technical complication with carotid angioplasty and carotid artery stenting (CAS). We evaluated the safety and efficacy of protection devices used during CAS by detecting new cerebral ischemic lesions using diffusion-weighted magnetic resonance imaging in 95 patients who underwent 98 CAS procedures: 34 using single PercuSurge GuardWire, 31 using double balloon protection, 15 using proximal flow reverse protection devices, 14 using Naviballoon, and 4 using filter anti-embolic devices. Diffusion-weighted imaging was performed preoperatively and postoperatively to evaluate the presence of any new embolic cerebral lesions. Postoperative diffusion-weighted imaging revealed 117 new ischemic lesions. Three patients had new ischemic stroke, two minor and one major, all ipsilateral to the treated carotid artery. The remaining patients had clinically silent ischemia. The incidence of new embolic lesions was lower using the proximal flow reverse protection device than with the double balloon protection (33% vs. 48.4%), but the volume of ipsilateral new ischemic lesions per patient was 136.6 mm(3) vs. 86.9 mm(3), respectively. Neuroprotection with Naviballoon yielded ipsilateral lesions of large volume (86.6 mm(3)) and higher number (5.7 lesions per patient) than using the filter anti-embolic device (34.8 mm(3) and 1 lesion per patient). New cerebral ischemic lesions after neuroprotected CAS are usually silent. The lower incidence of distal ischemia using proximal flow reverse and double balloon protection devices is limited by the larger volume and higher number of ischemic lesions.

NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice.

PubMed

Bardgett, Mark E; Boeckman, Ryan; Krochmal, Daniel; Fernando, Hiran; Ahrens, Rebecca; Csernansky, John G

2003-04-15

The interpretation of learning and memory deficits in transgenic mice has largely involved theories of NMDA receptor and/or hippocampal function. However, there is little empirical data that describes what NMDA receptors or the hippocampus do in mice. This research assessed the effects of different doses of the NMDA receptor antagonist, MK-801, or different-sized hippocampal lesions on several behavioral parameters in adult male C57Bl/6 mice. In the first set of experiments, different doses of MK-801 (0.05-0.3mg/kg, s.c.) were assayed in fear conditioning, shock sensitivity, locomotion, anxiety, and position habit reversal tests. Contextual and cued fear conditioning, and position habit reversal were impaired in a dose-dependent manner. Locomotor activity was increased immediately after injection of the highest dose of MK-801. A second set of experiments determined the behavioral effects of a moderate and large excitotoxic hippocampal lesion. Both lesions impaired contextual conditioning, while the larger lesion interfered with cued conditioning. Reversal learning was significantly diminished by the large lesion, while the moderate lesion had a detrimental effect at a trend level (P<0.10). These results provide important reference data for studies involving genetic manipulations of NMDA receptor or hippocampal function in mice. Furthermore, they serve as a basis for a non-transgenic mouse model of the NMDA receptor or hippocampal dysfunction hypothesized to occur in human cognitive disorders.

The Neural Basis of Reversible Sentence Comprehension: Evidence from Voxel-Based Lesion Symptom Mapping in Aphasia

ERIC Educational Resources Information Center

Thothathiri, Malathi; Kimberg, Daniel Y.; Schwartz, Myrna F.

2012-01-01

We explored the neural basis of reversible sentence comprehension in a large group of aphasic patients (n = 79). Voxel-based lesion symptom mapping revealed a significant association between damage in temporo-parietal cortex and impaired sentence comprehension. This association remained after we controlled for phonological working memory. We…

Pathology of callosal damage in ALS: An ex-vivo, 7 T diffusion tensor MRI study.

PubMed

Cardenas, Agustin M; Sarlls, Joelle E; Kwan, Justin Y; Bageac, Devin; Gala, Zachary S; Danielian, Laura E; Ray-Chaudhury, Abhik; Wang, Hao-Wei; Miller, Karla L; Foxley, Sean; Jbabdi, Saad; Welsh, Robert C; Floeter, Mary Kay

2017-01-01

The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres. FA of the body and genu was expressed as ratio to FA of the splenium, a region unaffected in ALS. After imaging, tissue sections of the same segments of the callosum were stained for markers of different tissue components. Coded image fields were rated for pathological changes by blinded raters. The FA body/FA splenium ratio was reduced in ALS patients compared to controls. Patchy areas of myelin pallor and cells immunostained for CD68, a microglial-macrophage marker, were only observed in the body of the callosum of ALS patients. Blinded ratings showed increased CD68 + microglial cells in the body of the corpus callosum in ALS patients, especially those with C9orf72 mutations, and increased reactive astrocytes throughout the callosum. Reduced FA of the corpus callosum in ALS results from complex changes in tissue microstructure. Callosal segments with reduced FA had large numbers of microglia-macrophages in addition to loss of myelinated axons and astrogliosis. Microglial inflammation contributed to reduced FA in ALS, and may contribute to a pro-inflammatory state, but further work is needed to determine their role.

BASOLATERAL AMYGDALA LESIONS AND SENSITIVITY TO REINFORCER MAGNITUDE IN CONCURRENT CHAINS SCHEDULES

PubMed Central

Helms, Christa M.; Mitchell, Suzanne H.

2008-01-01

Previous studies show that the basolateral amygdala (BLA) is required for behavior to adjust when the value of a reinforcer decreases after satiation or pairing with gastric distress. This study evaluated the effect of pre- or post-training excitotoxic lesions of the BLA on changes in preference with another type of contingency change, reinforcer magnitude reversal. Rats were trained to press left and right levers during a variable-interval choice phase for 50 µl or 150 µl sucrose delivered to consistent locations after a 16-s delay. Tones were presented during the first and last 2 s of the delay to reinforcement. The tone frequency predicted the magnitude of sucrose reinforcement in baseline conditions. All groups acquired stable preference for the lever on the large (150-µl) reinforcer side. However, nose poking during the delay to large reinforcement was highly accurate (i.e., to the reinforced side) for all groups except the rats with BLA lesions induced before training, suggesting impaired control of behavior by the tone. After the acquisition of stable preference, the locations of the reinforcer magnitudes were unpredictably reversed for a single session. Pre-training lesions blunted changes in preference when the reinforcer magnitudes were reversed. Lesions induced after stable preference was acquired, but prior to reversal, did not disrupt changes in preference. The data suggest that the BLA contributes to the adaptation of choice behavior following changes in reinforcer magnitude. Impaired learning about the tone-reinforcer magnitude relationships may have disrupted discrimination of the reinforcer magnitude reversal. PMID:18455812

Higher contact force during radiofrequency ablation leads to a much larger increase in edema as compared to chronic lesion size.

PubMed

Thomas, Samuel; Silvernagel, Josh; Angel, Nathan; Kholmovski, Eugene; Ghafoori, Elyar; Hu, Nan; Ashton, John; Dosdall, Derek J; MacLeod, Rob; Ranjan, Ravi

2018-05-18

Reversible edema is a part of any radiofrequency ablation but its relationship with contact force is unknown. The goal of this study was to characterize through histology and MRI, acute and chronic ablation lesions and reversible edema with contact force. In a canine model (n = 14), chronic ventricular lesions were created with a 3.5-mm tip ThermoCool SmartTouch (Biosense Webster) catheter at 25 W or 40 W for 30 seconds. Repeat ablation was performed after 3 months to create a second set of lesions (acute). Each ablation procedure was followed by in vivo T2-weighted MRI for edema and late-gadolinium enhancement (LGE) MRI for lesion characterization. For chronic lesions, the mean scar volumes at 25 W and 40 W were 77.8 ± 34.5 mm 3 (n = 24) and 139.1 ± 69.7 mm 3 (n = 12), respectively. The volume of chronic lesions increased (25 W: P < 0.001, 40 W: P < 0.001) with greater contact force. For acute lesions, the mean volumes of the lesion were 286.0 ± 129.8 mm 3 (n = 19) and 422.1 ± 113.1 mm 3 (n = 16) for 25 W and 40 W, respectively (P < 0.001 compared to chronic scar). On T2-weighted MRI, the acute edema volume was on average 5.6-8.7 times higher than the acute lesion volume and increased with contact force (25 W: P = 0.001, 40 W: P = 0.011). With increasing contact force, there is a marginal increase in lesion size but accompanied with a significantly larger edema. The reversible edema that is much larger than the chronic lesion volume may explain some of the chronic procedure failures. © 2018 Wiley Periodicals, Inc.

White matter correlates of sensory processing in autism spectrum disorders

PubMed Central

Pryweller, Jennifer R.; Schauder, Kimberly B.; Anderson, Adam W.; Heacock, Jessica L.; Foss-Feig, Jennifer H.; Newsom, Cassandra R.; Loring, Whitney A.; Cascio, Carissa J.

2014-01-01

Autism spectrum disorder (ASD) has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure. PMID:25379451

Corpus callosum integrity is affected by mood disorders and also by the suicide attempt history: A diffusion tensor imaging study.

PubMed

Cyprien, Fabienne; de Champfleur, Nicolas Menjot; Deverdun, Jérémy; Olié, Emilie; Le Bars, Emmanuelle; Bonafé, Alain; Mura, Thibault; Jollant, Fabrice; Courtet, Philippe; Artero, Sylvaine

2016-12-01

Some MRI studies have noted alterations in the corpus callosum (CC) white matter integrity of individuals with mood disorders and also in patients with suicidal behavior. We investigated the specific impact of suicidal behavior on CC integrity in mood disorders. CC structural changes were assessed by diffusion tensor imaging (DTI) in 121 women 18-50-year-old): 41 with bipolar disorder (BD), 50 with major depressive disorder (MDD) and 30 healthy controls (HC). Fractional anisotropy (FA) and DTI metrics were calculated for the genu, body and splenium of CC and compared in the three groups by MANCOVA. Then, they were re-analyzed relative to the suicide attempt history within the MDD and BD groups and to the suicide number/severity. FA values for the CC genu and body were lower in non-suicide attempters with BD than with MDD and in HC. Conversely, FA values for all CC regions were significantly lower in suicide attempters with BD than in HC. Finally, higher number of suicide attempts (>2) and elevated Suicidal Intent Scale score were associated with significant splenium alterations. Limitations include the cross-sectional design (non-causal study), the potential influence of medications and concerns about the generalizability to men. Genu and body are altered in non-suicide attempters with BD, while splenium is specifically altered in suicide attempters, independently from their psychiatric status. History of suicide attempts may be a source of heterogeneity in the association between CC alterations and BD and may partially explain the variable results of previous studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

PubMed Central

Garcia, Bonnie G.; Neely, M. Diana

2010-01-01

Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion–induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease. PMID:20118184

The role of pedunculopontine nucleus in choice behavior under risk

PubMed Central

Leblond, Mona; Sukharnikova, Tatyana; Yu, Chunxiu; Rossi, Mark A.; Yin, Henry H.

2014-01-01

The dopaminergic projections to the basal ganglia have long been implicated in reward guided behavior and decision making, yet little is known about the role of the posterior pedunculopontine nucleus (pPPN), a major source of excitatory input to the mesolimbic dopamine system. Here we studied the contributions of pPPN to decision making under risk, using excitoxic lesions and reversible inactivation in rats. Rats could choose between two options: a small but certain reward on one lever, or a large but uncertain reward on the other lever. The overall payoff associated with each choice is the same, but the reward variance (risk) associated with the risky choice is much higher. In Experiment 1, we showed that excitotoxic lesions of the pPPN before training did not affect acquisition of lever pressing. But whereas the controls strongly preferred the safe choice, the lesioned rats did not. In Experiment 2, we found that muscimol inactivation of the pPPN also reversibly altered choice behavior. These results show that permanent lesions or reversible inactivation of the pPPN both abolish risk aversion in decision making. PMID:24617747

Tips of the dual-lumen microcatheter-facilitated reverse wire technique in percutaneous coronary interventions for markedly angulated bifurcated lesions.

PubMed

Nomura, Tetsuya; Kikai, Masakazu; Hori, Yusuke; Yoshioka, Kenichi; Kubota, Hiroshi; Miyawaki, Daisuke; Urata, Ryota; Sugimoto, Takeshi; Keira, Natsuya; Tatsumi, Tetsuya

2018-04-01

In practical settings of percutaneous coronary intervention (PCI), we sometimes encounter difficulty in introducing a guidewire (GW) to the markedly angulated side branch (SB), and the reverse wire technique is considered as a last resort to overcome such a situation. We analyzed 12 cases that underwent PCI with dual-lumen microcatheter-facilitated reverse wire technique between January 2013 and July 2016. We retrospectively investigated the lesion's characteristics and the details of the PCI procedures, and discussed tips about the use of this technique. The SB that exhibits both a smaller take-off angle and a larger carina angle is considered to be the most suitable candidate for this technique. The first step of this technique involves the delivery of the reverse wire system to the target bifurcation. However, most cases exhibit significant stenosis proximal to the bifurcation, which often hampers the delivery of the reverse wire system. Because the sharply curved reverse wire system is easier to pass the stenosis as compared to the roundly curved system, we recommend a sharp curve should be adopted for this technique. On the other hand, it is sure that device delivery is much easier on the GW with a round curve as compared to that with a sharp curve. Therefore, it is important to modify the details of this procedure on a case-by-case basis according to the lesion's characteristics.

Rewarding brain stimulation reverses the disruptive effect of amygdala damage on emotional learning.

PubMed

Kádár, Elisabet; Ramoneda, Marc; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

2014-11-01

Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed. Copyright © 2014 Elsevier B.V. All rights reserved.

The Role of Frontal Cortical and Medial-Temporal Lobe Brain Areas in Learning a Bayesian Prior Belief on Reversals

PubMed Central

Jang, Anthony I.; Costa, Vincent D.; Rudebeck, Peter H.; Chudasama, Yogita; Murray, Elisabeth A.

2015-01-01

Reversal learning has been extensively studied across species as a task that indexes the ability to flexibly make and reverse deterministic stimulus–reward associations. Although various brain lesions have been found to affect performance on this task, the behavioral processes affected by these lesions have not yet been determined. This task includes at least two kinds of learning. First, subjects have to learn and reverse stimulus–reward associations in each block of trials. Second, subjects become more proficient at reversing choice preferences as they experience more reversals. We have developed a Bayesian approach to separately characterize these two learning processes. Reversal of choice behavior within each block is driven by a combination of evidence that a reversal has occurred, and a prior belief in reversals that evolves with experience across blocks. We applied the approach to behavior obtained from 89 macaques, comprising 12 lesion groups and a control group. We found that animals from all of the groups reversed more quickly as they experienced more reversals, and correspondingly they updated their prior beliefs about reversals at the same rate. However, the initial values of the priors that the various groups of animals brought to the task differed significantly, and it was these initial priors that led to the differences in behavior. Thus, by taking a Bayesian approach we find that variability in reversal-learning performance attributable to different neural systems is primarily driven by different prior beliefs about reversals that each group brings to the task. SIGNIFICANCE STATEMENT The ability to use prior knowledge to adapt choice behavior is critical for flexible decision making. Reversal learning is often studied as a form of flexible decision making. However, prior studies have not identified which brain regions are important for the formation and use of prior beliefs to guide choice behavior. Here we develop a Bayesian approach that formally characterizes learning set as a concept, and we show that, in macaque monkeys, the amygdala and medial prefrontal cortex have a role in establishing an initial belief about the stability of the reward environment. PMID:26290251

Selective aspiration or neurotoxic lesions of orbital frontal areas 11 and 13 spared monkeys’ performance on the object discrimination reversal task

PubMed Central

Kazama, Andy; Bachevalier, Jocelyne

2009-01-01

Damage to the orbital frontal cortex (OFC) has long been associated with reversal learning deficits in several species. In monkeys, this impairment follows lesions that include several OFC subfields. However, the different connectional patterns of OFC subfields together with neuroimaging data in humans have suggested that specific OFC areas play distinctive roles in processing information necessary to guide behavior (Kringelbach and Rolls, 2004; Barbas, 2007; Price, 2007). More specifically, areas 11 and 13 contribute to a sensory network, whereas medial areas 10, 14, and 25 are heavily connected to a visceromotor network. To examine the contribution of areas 11 and 13 to reversal learning, we tested monkeys with selective damage to these two OFC areas on two versions of the ODR task using either 1 or 5 discrimination problems. We compared their performance with that of sham-operated controls and of animals with neurotoxic amygdala lesions, which served as operated controls. Neither damage to areas 11 and 13 nor damage to the amygdala affected performance on the ODR tasks. The results indicate that areas 11 and 13 do not critically contribute to reversal learning and that adjacent damage to OFC subfields (10, 12, 14 and 25) could account for the ODR deficits found in earlier lesion studies. This sparing of reversal learning will be discussed in relation to deficits found in the same animals on tasks that measure behavioral modulation when relative value of affective (positive and negative) stimuli was manipulated. PMID:19261875

Numerical simulation of high intensity focused ultrasound temperature distribution for transcranial brain therapy

NASA Astrophysics Data System (ADS)

Zhang, Qian; Wang, Yizhe; Zhou, Wenzheng; Zhang, Ji; Jian, Xiqi

2017-03-01

To provide a reference for the HIFU clinical therapeutic planning, the temperature distribution and lesion volume are analyzed by the numerical simulation. The adopted numerical simulation is based on a transcranial ultrasound therapy model, including an 8 annular-element curved phased array transducer. The acoustic pressure and temperature elevation are calculated by using the approximation of Westervelt Formula and the Pennes Heat Transfer Equation. In addition, the Time Reversal theory and eliminating hot spot technique are combined to optimize the temperature distribution. With different input powers and exposure times, the lesion volume is evaluated based on temperature threshold theory. The lesion region could be restored at the expected location by the time reversal theory. Although the lesion volume reduces after eliminating the peak temperature in the skull and more input power and exposure time is required, the injury of normal tissue around skull could be reduced during the HIFU therapy. The prediction of thermal deposition in the skull and the lesion region could provide a reference for clinical therapeutic dose.

Posterior Reversible Encephalopathy Syndrome (PRES): Restricted Diffusion does not Necessarily Mean Irreversibility.

PubMed

Wagih, Alaa; Mohsen, Laila; Rayan, Moustafa M; Hasan, Mo'men M; Al-Sherif, Ashraf H

2015-01-01

Restricted diffusion is the second most common atypical presentation of PRES. This has a very important implication, as lesions with cytotoxic edema may progress to infarction. Several studies suggested the role of DWI in the prediction of development of infarctions in these cases. Other studies, however, suggested that PRES is reversible even with cytotoxic patterns. Our aim was to evaluate whether every restricted diffusion in PRES is reversible and what factors affect this reversibility. Thirty-six patients with acute neurological symptoms suggestive of PRES were included in our study. Inclusion criteria comprised imaging features of atypical PRES where DWI images and ADC maps show restricted diffusion. Patients were imaged with 0.2-T and 1.5-T machines. FLAIR images were evaluated for the severity of the disease and a FLAIR/DWI score was used. ADC values were selectively recorded from the areas of diffusion restriction. A follow-up MRI study was carried out in all patients after 2 weeks. Patients were classified according to reversibility into: Group 1 (reversible PRES; 32 patients) and Group 2 (irreversible changes; 4 patients). The study was approved by the University's research ethics committee, which conforms to the declaration of Helsinki. The age and blood pressure did not vary significantly between both groups. The total number of regions involved and the FLAIR/DWI score did not vary significantly between both groups. Individual regions did not reveal any tendency for the development of irreversible lesions. Similarly, ADC values did not reveal any significant difference between both groups. PRES is completely reversible in the majority of patients, even with restricted diffusion. None of the variables under study could predict the reversibility of PRES lesions. It seems that this process is individual-dependent.

Posterior Reversible Encephalopathy Syndrome (PRES): Restricted Diffusion does not Necessarily Mean Irreversibility

PubMed Central

Wagih, Alaa; Mohsen, Laila; Rayan, Moustafa M.; Hasan, Mo’men M.; Al-Sherif, Ashraf H.

2015-01-01

Summary Background Restricted diffusion is the second most common atypical presentation of PRES. This has a very important implication, as lesions with cytotoxic edema may progress to infarction. Several studies suggested the role of DWI in the prediction of development of infarctions in these cases. Other studies, however, suggested that PRES is reversible even with cytotoxic patterns. Our aim was to evaluate whether every restricted diffusion in PRES is reversible and what factors affect this reversibility. Material/Methods Thirty-six patients with acute neurological symptoms suggestive of PRES were included in our study. Inclusion criteria comprised imaging features of atypical PRES where DWI images and ADC maps show restricted diffusion. Patients were imaged with 0.2-T and 1.5-T machines. FLAIR images were evaluated for the severity of the disease and a FLAIR/DWI score was used. ADC values were selectively recorded from the areas of diffusion restriction. A follow-up MRI study was carried out in all patients after 2 weeks. Patients were classified according to reversibility into: Group 1 (reversible PRES; 32 patients) and Group 2 (irreversible changes; 4 patients). The study was approved by the University’s research ethics committee, which conforms to the declaration of Helsinki. Results The age and blood pressure did not vary significantly between both groups. The total number of regions involved and the FLAIR/DWI score did not vary significantly between both groups. Individual regions did not reveal any tendency for the development of irreversible lesions. Similarly, ADC values did not reveal any significant difference between both groups. Conclusions PRES is completely reversible in the majority of patients, even with restricted diffusion. None of the variables under study could predict the reversibility of PRES lesions. It seems that this process is individual-dependent. PMID:25960819

The neural basis of reversible sentence comprehension: Evidence from voxel-based lesion-symptom mapping in aphasia

PubMed Central

Thothathiri, Malathi; Kimberg, Daniel Y.; Schwartz, Myrna F.

2012-01-01

We explored the neural basis of reversible sentence comprehension in a large group of aphasic patients (N=79). Voxel-based lesion-symptom mapping revealed a significant association between damage in temporoparietal cortex and impaired sentence comprehension. This association remained after we controlled for phonological working memory. We hypothesize that this region plays an important role in the thematic or what-where processing of sentences. In contrast, we detected weak or no association between reversible sentence comprehension and the ventrolateral prefrontal cortex, which includes Broca’s area, even for syntactically complex sentences. This casts doubt on theories that presuppose a critical role for this region in syntactic computations. PMID:21861679

Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years.

PubMed

Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Ron, Maria; Penny, Sophie; Thompson, Alan J; Ciccarelli, Olga

2013-05-01

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Copyright © 2011 Wiley Periodicals, Inc.

Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults.

PubMed

Menegaux, Aurore; Meng, Chun; Neitzel, Julia; Bäuml, Josef G; Müller, Hermann J; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra M; Finke, Kathrin; Sorg, Christian

2017-04-15

Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of citicoline therapy on the network connectivity of the corpus callosum in patients with leukoaraiosis

PubMed Central

Feng, Liang; Jiang, Hong; Li, Yunxia; Teng, Fei; He, Yusheng

2017-01-01

Abstract This study aimed to investigate the effects of citicoline therapy on the network connectivity of the corpus callosum in patients with leukoaraiosis (LA) by diffusion tension imaging (DTI). A total of 30 LA patients with Fazekas score of 2 to 3 were voluntarily assigned into citicoline group (n = 14) and control group (n = 16). In citicoline group, citicoline was administered at 0.6 g/d for 1 year. In control group, central nervous system drugs should not be used, except for sleeping pills and antidepressants. Interventions for pre-existing diseases should be conducted in both groups. During the periods of citicoline therapy and post-treatment follow-up, cranial magnetic resonance imaging and DTI were routinely performed in these patients, and the genu, body, and splenium of corpus callosum were selected as the regions of interest (ROIs). The fractional anisotropy (FA) and mean diffusivity (MD) of each ROI were determined with PANDA software. On recruitment, there were no significant differences in the general characteristics, blood biochemical results, cognition function, and the FA and MD of the corpus callosum between 2 groups (P > 0.05). After 1-year treatment, the FA of the corpus callosum reduced gradually, but the MD of the corpus callosum tended to increased in both group, although significant differences were not observed. However, the reductions in FA of genu and splenium of corpus callosum in citicoline group were significantly lower than in control group (P < 0.05); the reductions in MD of genu, body, and splenium of corpus callosum in citicoline group were significantly lower than in control group (P < 0.05). In LA patients, the disruption of the network connectivity of the corpus callosum deteriorates over time. Citicoline treatment may delay the reduction in FA of corpus callosum, which might be beneficial for the improvement of network connectivity of the corpus callosum. PMID:28121935

Inter-hemispheric Functional Connectivity Changes with Corpus Callosum Morphology in Multiple Sclerosis

PubMed Central

Zito, Giancarlo; Luders, Eileen; Tomasevic, Leo; Lupoi, Domenico; Toga, Arthur W.; Thompson, Paul M.; Rossini, Paolo M.; Filippi, Maria M.; Tecchio, Franca

2014-01-01

Multiple sclerosis (MS) affects myelin sheaths within the central nervous system, concurring to cause brain atrophy and neurodegeneration as well as gradual functional disconnections. To explore early signs of altered connectivity in MS from a structural and functional perspective, the morphology of corpus callosum (CC) was correlated with a dynamic inter-hemispheric connectivity index. Twenty mildly disabled patients affected by a relapsing-remitting (RR) form of MS (EDSS ≤ 3.5) and 15 healthy subjects underwent structural MRI to measure CC thickness over 100 sections and electroencephalography to assess a spectral coherence index between primary regions devoted to hand control, at rest and during an isometric handgrip. In patients, an overall CC atrophy was associated with increased lesion load. A less efficacious inter-hemispheric coherence during movement was associated with CC atrophy in sections interconnecting homologous primary motor areas (anterior mid-body). In healthy controls, less efficacious inter-hemispheric coherence at rest was associated with a thinner CC splenium. Our data suggest that in mildly disabled RR-MS patients a covert impairment may be detected in the correlation between the structural (CC thickness) and functional (inter-hemispheric coherence) measures of homologous networks, whereas these two counterparts do not yet differ individually from controls. PMID:24486438

The behavior of chronic cats with lesions in the frontal association cortex.

PubMed

Warren, J M; Warren, H B; Akert, K

1972-01-01

Cats with lesions in the proreal and anterior sigmoid gyri and substantial but subtotal degeneration in the mediodorsal thalamic nucleus were studied for 6 years post-operatively. The control group consisted of normal cats matched for age and previous experience. The results reported here and in Warren's previous progress report indicate that frontal cortical lesions result in several behavioral changes in cats which are like those seen in rhesus monkeys after frontal ablations: impairments in discrimination reversal, double alternation and active avoidance learning, retardation in the rate of habituation to novel neutral stimuli, and a decrease in aggression in competitive social situations. Cats with larger frontal lesions made more errors in reversal learning than cats with smaller lesions. Frontal cats, unlike frontal rhesus monkeys, are not hyperactive post-operatively and retain some capacity for learning delayed response in the WGTA. It is impossible at present to tell whether these discrepancies reflect species differences in the organization of the frontal lobe system or whether the frontal cortex spared in this series of cats is sufficient to mediate delayed response and to prevent the occurrence of hyperactivity.

Diffusion-weighted imaging of the liver at 3 T using section-selection gradient reversal: emphasis on chemical shift artefacts and lesion conspicuity.

PubMed

Lee, J S; Kim, Y K; Jeong, W K; Choi, D; Lee, W J

2015-04-01

To assess the value of section-selection gradient reversal (SSGR) in liver diffusion-weighted imaging (DWI) by comparing it to conventional DWI with an emphasis on chemical shift artefacts and lesion conspicuity. Forty-eight patients (29 men and 19 women; age range 33-80 years) with 48 liver lesions underwent two DWI examinations using spectral presaturation with inversion recovery fat suppression with and without SSGR at 3 T. Two reviewers evaluated each DWI (b = 100 and b = 800 image) with respect to chemical shift artefacts and liver lesion conspicuity using five-point scales and performed pairwise comparisons between the two DWIs. The signal-to-noise ratio (SNR) of the liver and the lesion and the lesion-liver contrast-to-noise ratio (CNR) were also calculated. SSGR-DWI was significantly better than conventional DWI with respect to chemical shift artefacts and lesion conspicuity in both separate reviews and pairwise comparisons (p < 0.05). There were significant differences in the SNR of the liver (b = 100 and b = 800 images) and lesion (b = 800) between SSGR-DWI and conventional DWI (p < 0.05). Applying the SSGR method to DWI using SPIR fat suppression at 3 T could significantly reduce chemical shift artefacts without incurring additional acquisition time or SNR penalties, which leads to increased conspicuity of focal liver lesions. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Laparoscopic pancreaticoduodenectomy via a reverse-''V'' approach with four ports: initial experience and perioperative outcomes.

PubMed

Liu, Zhao; Yu, Mu-Chuan; Zhao, Rui; Liu, Yan-Feng; Zeng, Jian-Ping; Wang, Xian-Qiang; Tan, Jing-Wang

2015-02-07

To evaluate the feasibility, safety, and efficacy of laparoscopic pancreaticoduodenectomy (LPD) using a reverse-"V" approach with four ports. This is a retrospective study of selected patients who underwent LPD at our center between April 2011 and April 2012. The following data were collected and reviewed: patient characteristics, tumor histology, surgical outcome, resection margins, morbidity, and mortality. All patients were thoroughly evaluated preoperatively by complete hematologic investigations, triple-phase helical computed tomography, upper gastrointestinal endoscopy, and biopsy of ampullary lesions (when present). Magnetic resonance cholangiopancreatography was performed for doubtful cases of lower common bile duct lesions. There was no perioperative mortality. LPD was performed with tumor-free margins in all patients, including patients with pancreatic ductal adenocarcinoma (n = 6), ampullary carcinoma (n = 6), intra-ductal papillary mucinous neoplasm (n = 2), pancreatic cystadenocarcinoma (n = 2), pancreatic head adenocarcinoma (n = 3), and bile duct cancer (n = 2). The mean patient age was 65 years (range, 42-75 years). The median blood loss was 240 mL, and the mean operative time was 368 min. LPD using a reverse-"V" approach can be performed safely and yields good results in elective patients. Our preliminary experience showed that LDP can be performed via a reverse-"V" approach. This approach can be used to treat localized malignant lesions irrespective of histopathology.

Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.

PubMed

Jayasekeran, Vanoo; Singh, Salil; Tyrrell, Pippa; Michou, Emilia; Jefferson, Samantha; Mistry, Satish; Gamble, Ed; Rothwell, John; Thompson, David; Hamdy, Shaheen

2010-05-01

Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038). This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Metronidazole-induced reversible cerebellar lesions and peripheral neuropathy].

PubMed

Toumi, S; Hammouda, M; Essid, A; Medimagh, L; Slamia, L Ben; Laouani-Kechrid, C

2009-12-01

Metronidazole is a widely prescribed treatment for amoebic and anaerobic germ infections. Its neurologic toxicity is rare but can be serious. We report the case of a 27-year-old male patient, treated with metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect of the cerebellar lesions in addition to their reversibility after treatment cessation led to the diagnosis of metronidazole induced neurologic toxicity. The occurrence of neurologic disorders in patients treated with metronidazole must suggest drug toxicity and lead to cessation of treatment.

Handedness and corpus callosal morphology in Williams syndrome.

PubMed

Martens, Marilee A; Wilson, Sarah J; Chen, Jian; Wood, Amanda G; Reutens, David C

2013-02-01

Williams syndrome is a neurodevelopmental genetic disorder caused by a hemizygous deletion on chromosome 7q11.23, resulting in atypical brain structure and function, including abnormal morphology of the corpus callosum. An influence of handedness on the size of the corpus callosum has been observed in studies of typical individuals, but handedness has not been taken into account in studies of callosal morphology in Williams syndrome. We hypothesized that callosal area is smaller and the size of the splenium and isthmus is reduced in individuals with Williams syndrome compared to healthy controls, and examined age, sex, and handedness effects on corpus callosal area. Structural magnetic resonance imaging scans were obtained on 25 individuals with Williams syndrome (18 right-handed, 7 left-handed) and 25 matched controls. We found that callosal thickness was significantly reduced in the splenium of Williams syndrome individuals compared to controls. We also found novel evidence that the callosal area was smaller in left-handed participants with Williams syndrome than their right-handed counterparts, with opposite findings observed in the control group. This novel finding may be associated with LIM-kinase hemizygosity, a characteristic of Williams syndrome. The findings may have significant clinical implications in future explorations of the Williams syndrome cognitive phenotype.

Characterizing populations and searching for diagnostics via elastic registration of MRI images

NASA Astrophysics Data System (ADS)

Pettey, David; Gee, James C.

2001-07-01

Given image data from two distinct populations and a family of functions, we find the scalar discriminant function which best discriminates between the populations. The goals are two-fold: first, to construct a discriminant function which can accurately and reliably classify subjects via the image data. Second, the best discriminant allows us to see which features in the images distinguish between the populations; these features can guide us to finding characteristic differences between the two groups even if these differences are not sufficient to perform classification. We apply our method to mid-sagittal MRI sections of the corpus callosum from 34 males and 52 females. While we are not certain of the ability of the derived discriminant function to perform sex classification, we find that regions in the anterior of the corpus callosum do appear to be more important for the discriminant function than other regions. This indicates there may be significant differences in the relative size of the splenium in males and females, as has been reported elsewhere. More notably, we applied previous methods which support this view on our larger data set, but found that these methods no longer show statistically significant differences between the male and female splenium.

A systematic review and meta-analysis of tract-based spatial statistics studies regarding attention-deficit/hyperactivity disorder.

PubMed

Chen, Lizhou; Hu, Xinyu; Ouyang, Luo; He, Ning; Liao, Yi; Liu, Qi; Zhou, Ming; Wu, Min; Huang, Xiaoqi; Gong, Qiyong

2016-09-01

Diffusion tensor imaging (DTI) studies that use tract-based spatial statistics (TBSS) have demonstrated the microstructural abnormalities of white matter (WM) in patients with attention-deficit/hyperactivity disorder (ADHD); however, robust conclusions have not yet been drawn. The present study integrated the findings of previous TBSS studies to determine the most consistent WM alterations in ADHD via a narrative review and meta-analysis. The literature search was conducted through October 2015 to identify TBSS studies that compared fractional anisotropy (FA) between ADHD patients and healthy controls. FA reductions were identified in the splenium of the corpus callosum (CC) that extended to the right cingulum, right sagittal stratum, and left tapetum. The first two clusters retained significance in the sensitivity analysis and in all subgroup analyses. The FA reduction in the CC splenium was negatively associated with the mean age of the ADHD group. We hypothesize that, in addition to the fronto-striatal-cerebellar circuit, the disturbed WM matter tracts that integrate the bilateral hemispheres and posterior-brain circuitries play a crucial role in the pathophysiology of ADHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ventricular tachyarrhythmia-related basal cardiomyopathy in rabbits with vagal stimulation--a novel experimental model for inverted Takotsubo-like cardiomyopathy.

PubMed

Takato, Tetsuya; Ashida, Terunao; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

2010-07-01

Electrical stimulation of the intact (unsectioned) cervical vagus in rabbits frequently provokes ventricular tachyarrhythmias that are often accompanied by mitral regurgitation. Unique pathological lesions often arise on the mitral valve, papillary muscles, and mitral annulus (mitral complex), the latter two of which become swollen and stiffened. These lesions are reversible in nature. Previous studies have essentially ignored the basal portion except for the mitral annulus. Therefore, the present study examined pathological lesions on the left ventricular basal portion in rabbits. The intact right vagal nerves of 20 anesthetized rabbits were repeatedly electrically stimulated under electrocardiographic monitoring. Colloidal carbon (lml) was injected intravenously immediately after the end of the stimulation and all animals were killed 1 week later. Pathological lesions were identified as carbon deposits visible at gross examination. Ventricular bigeminy was induced after vagal stimulation in 15 (75%) of the 20 rabbits. Pathological lesions were evident on the basal portion in 16 (80%) and on the mitral valve and papillary muscles of 15 (75%) of the 20 rabbits. Ventricular bigeminy was closely associated with the development of the pathological lesions, which were rarely observed on the ventricular apex. Cardiomyopathic lesions involving the basal portion and mitral complex were frequently induced in rabbits by vagal stimulation. These lesions bear a close similarity in distribution and reversibility to inverted Takotsubo cardiomyopathy. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Relationship between Iron Accumulation and White Matter Injury in Multiple Sclerosis: A Case-Control Study

PubMed Central

Raz, Eytan; Branson, Brittany; Jensen, Jens H.; Bester, Maxim; Babb, James S.; Herbert, Joseph; Grossman, Robert I.; Inglese, Matilde

2015-01-01

PURPOSE Despite the increasing development and applications of iron imaging, the pathophysiology of iron accumulation in multiple sclerosis (MS), and its role in disease progression and development of clinical disability, is poorly understood. The aims of our study were to determine the presence and extent of iron in T2 visible lesions and gray and white matter using magnetic field correlation (MFC) MRI and correlate with microscopic white matter (WM) injury as measured by diffusion tensor imaging (DTI). MATERIALS AND METHODS This is a case-control study incuding a series of 31 patients with clinically definite MS. The mean age was 39 years [standard deviation (SD)=9.55], they were 11 males and 20 females, with a disease duration average of 3 years (range 0-13) and a median EDSS of 2 (0-4.5). Seventeen healthy volunteers (6 males and 11 females) with a mean age of 36 years (SD=11.4) were recruited. All subjects underwent MR imaging on a 3T scanner using T2-weighted sequence, 3D T1 MPRAGE, MFC, single-shot DTI and postcontrast T1. T2-lesion volumes, brain volumetry, DTI parameters and iron quantification were calculated and multiple correlations were exploited. RESULTS Increased MFC was found in the putamen (p=0.061), the thalamus (p=0.123), the centrum semiovale (p=0.053), globus pallidus (p=0.008) and gray matter (GM) (p=0.004) of MS patients compared to controls. The mean lesional MFC was 121 s−2 (SD=67), significantly lower compared to the GM MFC (<0.0001). The GM mean diffusivity (MD) was inversely correlated with the MFC in the centrum semiovale (p<0.001), and in the splenium of the corpus callosum (p<0.001). CONCLUSION Patients with MS have increased iron in the globus pallidus, putamen and centrum with a trend toward increased iron in all the brain structures. Quantitative iron evaluation of WM and GM may improve the understanding of MS pathophysiology, and might serve as a surrogate marker of disease progression. PMID:25416468

Reverse smokers's and changes in oral mucosa. Department of Sucre, Colombia.

PubMed

Alvarez Gómez, Gloria-J; Alvarez Martínez, Efraín; Jiménez Gómez, Raúl; Mosquera Silva, Yolanda; Gaviria Núñez, Angela María; Garcés Agudelo, Adriana; Alonso Duque, Alexander; Zabala Castaño, Alexander; Echeverri González, Elizabeth; Isaac Millán, Melissa; Ramírez Ossa, Diana

2008-01-01

This work is intended to establish the prevalence of reverse smokers at the villages of Hato Nuevo, San Francisco and Cayo de Palma, Department of Sucre, Colombia, characterizing their socio-culture conditions, clinical and histological changes in the oral mucosa. A descriptive study was done through a home to home inquiry to select the people with inclusion criteria for a posterior clinical test and a biopsy of the affected oral mucosa. Reverse smokers's prevalence was from the 15%, mainly women (p<0.001) with an age average of 59.3 years. The lesions were classified clinically in mild, moderate and severe changes. Tongue moderate lesions presented the higher frequency (80%), followed by severe lesions on palate (74%). Oral cancer prevalence was 10.8% in the San Francisco village and 18.2% in Cayo de Palma village, no new cases were reported in Hato Nuevo village. This was the highest prevalence reported in comparison with other studies with similar population. The clinical and histological findings agree with the reported in literature, no relation was found between the degree of clinical severity and the dysplasia itself. Cases of oral submucous fibrosis-like lesions were found, which had never been reported in Latin America. Further studies are required in order to decrease the morbidity for this habit and to identify other related risk factors.

Post-Training Reversible Inactivation of the Hippocampus Enhances Novel Object Recognition Memory

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Hawk, Joshua D.; Abel, Ted; Havekes, Robbert

2010-01-01

Research on the role of the hippocampus in object recognition memory has produced conflicting results. Previous studies have used permanent hippocampal lesions to assess the requirement for the hippocampus in the object recognition task. However, permanent hippocampal lesions may impact performance through effects on processes besides memory…

Prehension Movements in a Patient (AC) with Posterior Parietal Cortex Damage and Posterior Callosal Section

ERIC Educational Resources Information Center

Frak, Victor; Paulignan, Yves; Jeannerod, Marc; Michel, Francois; Cohen, Henri

2006-01-01

Prehension movements of the right hand were recorded in a right-handed man (AC), with an injury to the left posterior parietal cortex (PPC) and with a section of the left half of the splenium. The kinematic analysis of AC's grasping movements in direct and perturbed conditions was compared to that of five control subjects. A novel effect in…

Reversible MRI lesions after seizures.

PubMed

Aykut-Bingol, C; Tekin, S; Ince, D; Aktan, S

1997-06-01

After generalized or partial seizures, transient lesions may appear on magnetic resonance (MR) images. The mechanisms of MR changes might be a defect in cerebral autoregulation and blood-brain permeability. We report a patient with partial and secondary generalized tonic-clonic seizures. After her first seizure which was generalized tonic-clonic in nature, we detected multiple high signal intensities over the frontal cortical area on proton density images which were enhanced with gadolinium on T1-weighted images. The first and repeated EEGs showed no abnormalities or epileptic discharges. We started carbamezapine (600 mg/d) and excluded systemic diseases like vasculitis, infections, aetiological factors causing cerebrovascular diseases. In the follow-up, she was seizure free under antiepileptic therapy and no other neurological deficit. Repeated MR scans after 24 months from her first seizure revealed no pathologic signal intensities. Although the pathophysiology is unknown, recognition of reversible lesions helps diagnostic and therapeutic approaches to abnormal MR findings after seizures.

Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

PubMed

Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

2014-04-01

The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats.

PubMed

Prkacin, I; Aralica, G; Perovic, D; Separovic, J; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Ziger, T; Anic, T; Sikiric, P; Seiwerth, S; Staresinic, M; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sjekavica, I; Sebecic, B; Boban-Blagaic, A; Ivasovic, Z

2001-01-01

Unlike severe gastric damage acutely induced by ethanol administration in rat, the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28 g/kg b.w.) given in drinking water, producing liver lesions and portal hypertension, is far less investigated. Therefore, focus was on the antiulcer effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in variety of gastrointestinal lesions models (10 microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They were given once daily (1) throughout 10 days preceding alcohol consumption, (2) since beginning of alcohol drinking till the end of the study, (3) throughout the last month of alcohol consumption, 2 months after alcohol drinking had been initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1), (2)] or with respect to therapeutic effect of medication before medication or at the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may prevent gastric lesion development if given prophylactically, before alcohol drinking. Likewise, they attenuate the lesion appearance given once daily throughout the drinking period. Importantly, when given therapeutically, they may antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine and propranol may prevent, attenuate or reverse the gastric lesions appearance in chronically alcohol drinking rats, and may be used for further therapy, while the other studies showed that their effect (except to ranitidine) is parallel with their beneficial effect on liver lesion and portal hypertension.

RADIATION-CAUSED CYTOCHEMICAL CHANGES IN NEURONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kagan, E.H.; Brownson, R.H.; Suter, D.B.

1962-09-01

The acute effects of ionizing radiation on the brain of rats were evaluated by using the acid phosphatase method of Gomori. Head irradiation was carried out with 1000-kv x rays at dose rates of 250 to 600 r/min and doses of 1500 to 10,000 r. The brains were examined 3 hr to 4 months later. The observed acute behavioral changes of apathy and sluggishness correlated with alterations in acidphosphatase-containing particles, which showed increased size and conglomeration in cortical neurons and especially Purkinje cells of the cerebellum. This early cytochemical effect of radiation was not noted with cresyl fast violet ormore » periodic acid-Schiff-stained material. The alterations were limited to ganglion cells; no glial or vascular lesions were noted by any staining procedure. In the Purkinje cells at higher dose ranges, up to one-half of the cells showed alterations in the form of swelling and conglomeration of the acid phosphatase particles, as well as diffuse cytoplasrnic staining. These alterations in acid-phosphatasecontaining particles were similar to changes in rat brains subjected to anoxic and anoxic-ischemic conditions, autolysis, and injection of diphtheria toxin. There was also a striking similarity between these changes and alterations in kidney and liver lysosomes as a result of experimental hydronephrosis. Animals killed four months after irradiation demonstrated the reversible nature of the lesion, which is correlated with reports of an initial reversible behavioral syndrome. The described cytochemical lesion is interpreted as morphological evidence of cell damage or altered cellular metabolism and not as a specific lesion caused by x irradiation. The apparent reversibility of the lesion and the fact that several different mechanisms have all demonstrated similar effects on acid-phosphatasecontaining particles in brain, kidney, and liver further point toward its nonspecific nature. (H.H.D.)« less

[Facial nerve injuries cause changes in central nervous system microglial cells].

PubMed

Cerón, Jeimmy; Troncoso, Julieta

2016-12-01

Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development

PubMed Central

Watari, Jiro; Chen, Nancy; Amenta, Peter S; Fukui, Hirokazu; Oshima, Tadayuki; Tomita, Toshihiko; Miwa, Hiroto; Lim, Kheng-Jim; Das, Kiron M

2014-01-01

Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the “point of no return” and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions. PMID:24833876

Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development.

PubMed

Watari, Jiro; Chen, Nancy; Amenta, Peter S; Fukui, Hirokazu; Oshima, Tadayuki; Tomita, Toshihiko; Miwa, Hiroto; Lim, Kheng-Jim; Das, Kiron M

2014-05-14

Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the "point of no return" and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.

The role of abnormalities in the corpus callosum in social cognition deficits after Traumatic Brain Injury.

PubMed

McDonald, Skye; Rushby, Jacqueline A; Dalton, Katie I; Allen, Samantha K; Parks, Nicklas

2018-08-01

The corpus callosum (CC) is vulnerable to severe traumatic brain injury (TBI). Social cognition requires integration of non-verbal and verbal information in order to understand social behaviour and may be compromised if the CC is damaged. 17 adults with severe, chronic TBI and 17 control participants underwent structural MRI and Diffusion Tensor Imaging. A region of interest analysis examined fractional anisotropy (FA) and mean diffusivity (MD) across regions of the CC. Performance on The Awareness of Social Inference Test (TASIT): part 1 (emotion recognition) and parts 2 and 3 (social inference), was examined in relation to FA and MD. Across participants, higher genu FA values were related to higher TASIT part 3 scores. Increased splenium FA was associated with better performance for TASIT parts 1-3. There was no association between DTI values and TASIT in the controls alone. In the TBI group, FA of the genu and splenium was correlated with TASIT part 3. The pattern of performance was similar when controlling for non-social cognitive ability. In conclusion, social information is complex and multi-modal requiring inter-hemispheric connection. People with TBI, regardless of focal grey matter injury, may lose social cognitive ability due to trauma related changes to the corpus callosum.

Medial prefrontal serotonin in the rat is involved in goal-directed behaviour when affect guides decision making.

PubMed

van der Plasse, Geoffrey; La Fors, Sabrina S B M; Meerkerk, Dorie T J; Joosten, Ruud N J M A; Uylings, Harry B M; Feenstra, Matthijs G P

2007-12-01

Across species, serotonin (5-HT) depletion in the prefrontal cortex (PFC) has been shown to cause impaired performance on tests of cognitive flexibility and the processing of affective information (e.g. information with an 'emotional' content). While recent work has explored the specific role of the orbital PFC herein, the role of the medial PFC remains unclear. The aim of our current experiments was to study the role of medial PFC 5-HT in both the processing of affective information and reversal learning across stimulus modalities. To this end, we selectively destroyed 5-HT terminals in the medial PFC of male Wistar rats by means of local infusion of the toxin 5,7-dihydroxytryptamine. Both control and lesioned animals were tested in two reversal learning paradigms with either spatial or odour cues and an affective switch from non-preferred to preferred food rewards. Our results indicate that a pellet switch during reversal learning impaired performance in control animals but not in lesioned animals, independent of the stimulus modality. These results indicate that lesioned animals are not guided in their behaviour by the affective value of the reward like intact animals and thus that medial prefrontal 5-HT is needed for affective processing in goal-directed behaviour.

Lesion Analysis of Cortical Regions Associated with the Comprehension of Nonreversible and Reversible Yes/No Questions

ERIC Educational Resources Information Center

Race, David S.; Ochfeld, Elisa; Leigh, Richard; Hillis, Argye E.

2012-01-01

We investigated the association between yes/no sentence comprehension and dysfunction in anterior and posterior left-hemisphere cortical regions in acute stroke patients. More specifically, we manipulated whether questions were Nonreversible (e.g., Are limes sour?) or Reversible (e.g., Is a horse larger than a dog?) to investigate the regions…

Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: the role of the infralimbic cortex in context generalization

PubMed Central

Ashwell, Rachel; Ito, Rutsuko

2014-01-01

The prelimbic and infralimbic regions of the rat medial prefrontal cortex (mPFC) are important components of the limbic cortico-striatal circuit, receiving converging projections from the hippocampus (HPC) and amygdala. Mounting evidence points to these regions having opposing roles in the regulation of the expression of contextual fear and context-induced cocaine-seeking. To investigate this functional differentiation in motivated behavior further, this study employed a novel radial maze task previously shown to be dependent on the integrity of the hippocampus and its functional connection to the nucleus accumbens (NAc) shell, to investigate the effects of selective excitotoxic lesions of the prelimbic (PL) and infralimbic (IL) upon the spatial contextual control over reward learning. To this end, rats were trained to develop discriminative responding towards a reward-associated discrete cue presented in three out of six spatial locations (3 arms out of 6 radial maze arms), and to avoid the same discrete cue presented in the other three spatial locations. Once acquired, the reward contingencies of the spatial locations were reversed, such that responding to the cue presented in a previously rewarded location was no longer rewarded. Furthermore, the acquisition of spatial learning was probed separately using conditioned place preference (CPP) and the monitoring of arm selection at the beginning of each training session. Lesions of the PL transiently attenuated the acquisition of the initial cue approach training and spatial learning, while leaving reversal learning intact. In contrast, IL lesions led to a significantly superior performance of spatial context-dependent discriminative cue approach and reversal learning, in the absence of a significant preference for the new reward-associated spatial locations. These results indicate that the PL and IL have functionally dissociative, and potentially opposite roles in the regulation of spatial contextual control over appetitive learning. PMID:24616678

Differential Impact of Posterior Lesions in the Left and Right Hemisphere on Visual Category Learning and Generalization to Contrast Reversal

ERIC Educational Resources Information Center

Langguth, Berthold; Juttner, Martin; Landis, Theodor; Regard, Marianne; Rentschler, Ingo

2009-01-01

Hemispheric differences in the learning and generalization of pattern categories were explored in two experiments involving sixteen patients with unilateral posterior, cerebral lesions in the left (LH) or right (RH) hemisphere. In each experiment participants were first trained to criterion in a supervised learning paradigm to categorize a set of…

Pramipexole but not imipramine or fluoxetine reverses the "depressive-like" behaviour in a rat model of preclinical stages of Parkinson's disease.

PubMed

Berghauzen-Maciejewska, Klemencja; Kuter, Katarzyna; Kolasiewicz, Wacław; Głowacka, Urszula; Dziubina, Anna; Ossowska, Krystyna; Wardas, Jadwiga

2014-09-01

Depression is a frequent comorbid disorder in Parkinson's disease and may antedate its motor symptoms. However, mechanisms underlying Parkinson's disease-associated depression are unknown and its current medication is insufficient. The aim of the present study was to compare antidepressant-like effects of imipramine, fluoxetine and pramipexole in a model of preclinical stages of Parkinson's disease in rats. 6-Hydroxydopamine was bilaterally injected into the ventrolateral region of the caudate-putamen in rats. This treatment induced moderate decreases in the levels of dopamine and its metabolites in the caudate-putamen, nucleus accumbens and frontal cortex and reduced the density of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta and ventral tegmental area. The lesion increased immobility measured in the forced swimming test without influencing locomotor activity. Chronic (13 days) administration of pramipexole (1mg/kg sc/twice a day) reversed prolongation of the immobility time in lesioned animals but did not stimulate their locomotion. Chronic pramipexole activated dopaminergic transmission in the brain structures which might contribute to its effectiveness in the forced swimming test. In contrast, the 13-day administration of imipramine (10mg/kg ip/day) and fluoxetine (10mg/kg ip/day) did not shorten the immobility time in lesioned rats but reduced their locomotion. The present study indicates that already a moderate lesion of dopaminergic neurons induces "depressive-like" behaviour in animals which is reversed by chronic administration of the antiparkinsonian drug, pramipexole. Copyright © 2014 Elsevier B.V. All rights reserved.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.

PubMed

Kozić, Duško B; Petrović, Igor; Svetel, Marina; Pekmezović, Tatjana; Ragaji, Aleksandar; Kostić, Vladimir S

2014-11-01

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

All-optical photoacoustic imaging and detection of early-stage dental caries

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

2015-02-01

Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

Spatial Discrimination Reversal Learning in Weanling Rats Is Impaired by Striatal Administration of an NMDA-Receptor Antagonist

ERIC Educational Resources Information Center

Watson, Deborah J.; Stanton, Mark E.

2009-01-01

The striatum plays a major role in both motor control and learning and memory, including executive function and "behavioral flexibility." Lesion, temporary inactivation, and infusion of an N-methyl-d-aspartate (NMDA)-receptor antagonist into the dorsomedial striatum (dmSTR) impair reversal learning in adult rats. Systemic administration of MK-801…

Associations between prenatal, childhood, and adolescent stress and variations in white-matter properties in young men.

PubMed

Jensen, Sarah K G; Pangelinan, Melissa; Björnholm, Lassi; Klasnja, Anja; Leemans, Alexander; Drakesmith, Mark; Evans, C J; Barker, Edward D; Paus, Tomáš

2017-10-21

Previous studies have shown that both pre- and post-natal adversities, the latter including exposures to stress during childhood and adolescence, explain variation in structural properties of white matter (WM) in the brain. While previous studies have examined effects of independent stress exposures within one developmental period, such as childhood, we examine effects of stress across development using data from a prospective longitudinal study. More specifically, we ask how stressful events during prenatal development, childhood, and adolescence relate to variation in WM properties in early adulthood in young men recruited from a birth cohort. Using data from 393 mother-son pairs from a community-based birth cohort from England (Avon Longitudinal Study of Parents and Children), we examined how stressful life events relate to variation in different structural properties of WM in the corpus callosum and across the whole brain in early adulthood in men aged 18-21 years. We distinguish between stress occurring during three developmental periods: a) prenatal maternal stress, b) postnatal stress within the first four years of life, c) stress during adolescence (age 12-16 years). To obtain a comprehensive quantification of variation in WM, we assess structural properties of WM using four different measures, namely fractional anisotropy (FA), mean diffusivity (MD), magnetization transfer ratio (MTR) and myelin water fraction (MWF). The developmental model shows that prenatal stress is associated with lower MTR and MWF in the genu and/or splenium of the corpus callosum, and with lower MTR in global (lobar) WM. Stress during early childhood is associated with higher MTR in the splenium, and stress during adolescence is associated with higher MTR in the genu and lower MD in the splenium. We see no associations between postnatal stress and variation in global (lobar) WM. The current study found evidence for independent effects of stress on WM properties during distinct neurodevelopmental periods. We speculate that these independent effects are due to differences in the developmental processes unfolding at different developmental time points. We suggest that associations between prenatal stress and WM properties may relate to abnormalities in neurogenesis, affecting the number and density of axons, while postnatal stress may interfere with processes related to myelination or radial growth of axons. Potential consequences of prenatal glucocorticoid exposure should be considered in obstetric care. Copyright © 2017 Elsevier Inc. All rights reserved.

Korsakoff syndrome from retrochiasmatic suprasellar lesions: rapid reversal after relief of cerebral compression in 4 cases.

PubMed

Savastano, Luis E; Hollon, Todd C; Barkan, Ariel L; Sullivan, Stephen E

2018-06-01

Korsakoff syndrome is a chronic memory disorder caused by a severe deficiency of thiamine that is most commonly observed in alcoholics. However, some have proposed that focal structural lesions disrupting memory circuits-in particular, the mammillary bodies, the mammillothalamic tract, and the anterior thalamus-can give rise to this amnestic syndrome. Here, the authors present 4 patients with reversible Korsakoff syndromes caused by suprasellar retrochiasmatic lesions compressing the mammillary bodies and adjacent caudal hypothalamic structures. Three of the patients were found to have large pituitary macroadenomas in their workup for memory deficiency and cognitive decline with minimal visual symptoms. These tumors extended superiorly into the suprasellar region in a retrochiasmatic position and caused significant mass effect in the bilateral mammillary bodies in the base of the brain. These 3 patients had complete and rapid resolution of amnestic problems shortly after initiation of treatment, consisting of resection in 1 case of nonfunctioning pituitary adenoma or cabergoline therapy in 2 cases of prolactinoma. The fourth patient presented with bizarre and hostile behavior along with significant memory deficits and was found to have a large cystic craniopharyngioma filling the third ventricle and compressing the midline diencephalic structures. This patient underwent cyst fenestration and tumor debulking, with a rapid improvement in his mental status. The rapid and dramatic memory improvement observed in all of these cases is probably due to a reduction in the pressure imposed by the lesions on structures contiguous to the third ventricle, rather than a direct destructive effect of the tumor, and highlights the essential role of the caudal diencephalic structures-mainly the mammillary bodies-in memory function. In summary, large pituitary lesions with suprasellar retrochiasmatic extension and third ventricular craniopharyngiomas can cause severe Korsakoff-like amnestic syndromes, probably because of bilateral pressure on or damage to mammillary bodies, anterior thalamic nuclei, or their major connections. Neuropsychiatric symptoms may rapidly and completely reverse shortly after initiation of therapy via surgical decompression of tumors or pharmacological treatment of prolactinomas. Early identification of these lesions with timely treatment can lead to a favorable prognosis for this severe neuropsychiatric disorder.

The Integrity of the Corpus Callosum Mitigates the Impact of Blood Pressure on the Ventral Attention Network and Information Processing Speed in Healthy Adults

PubMed Central

Wong, Nichol M. L.; Ma, Ernie Po-Wing; Lee, Tatia M. C.

2017-01-01

Hypertension is a risk factor for cognitive impairment in older age. However, evidence of the neural basis of the relationship between the deterioration of cognitive function and elevated blood pressure is sparse. Based on previous research, we speculate that variations in brain connectivity are closely related to elevated blood pressure even before the onset of clinical conditions and apparent cognitive decline in individuals over 60 years of age. Forty cognitively healthy adults were recruited. Each received a blood pressure test before and after the cognitive assessment in various domains. Diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) data were collected. Our findings confirm that elevated blood pressure is associated with brain connectivity variations in cognitively healthy individuals. The integrity of the splenium of the corpus callosum is closely related to individual differences in systolic blood pressure. In particular, elevated systolic blood pressure is related to resting-state ventral attention network (VAN) and information processing speed. Serial mediation analyses have further revealed that lower integrity of the splenium statistically predicts elevated systolic blood pressure, which in turn predicts weakened functional connectivity (FC) within the VAN and eventually poorer processing speed. The current study sheds light on how neural correlates are involved in the impact of elevated blood pressure on cognitive functioning. PMID:28484386

Medial prefrontal serotonin in the rat is involved in goal-directed behaviour when affect guides decision making

PubMed Central

La Fors, Sabrina S. B. M.; Meerkerk, Dorie T. J.; Joosten, Ruud N. J. M. A.; Uylings, Harry B. M.; Feenstra, Matthijs G. P.

2007-01-01

Rationale Across species, serotonin (5-HT) depletion in the prefrontal cortex (PFC) has been shown to cause impaired performance on tests of cognitive flexibility and the processing of affective information (e.g. information with an ‘emotional’ content). While recent work has explored the specific role of the orbital PFC herein, the role of the medial PFC remains unclear. Objectives The aim of our current experiments was to study the role of medial PFC 5-HT in both the processing of affective information and reversal learning across stimulus modalities. Materials and methods To this end, we selectively destroyed 5-HT terminals in the medial PFC of male Wistar rats by means of local infusion of the toxin 5,7-dihydroxytryptamine. Both control and lesioned animals were tested in two reversal learning paradigms with either spatial or odour cues and an affective switch from non-preferred to preferred food rewards. Results Our results indicate that a pellet switch during reversal learning impaired performance in control animals but not in lesioned animals, independent of the stimulus modality. Conclusion These results indicate that lesioned animals are not guided in their behaviour by the affective value of the reward like intact animals and thus that medial prefrontal 5-HT is needed for affective processing in goal-directed behaviour. PMID:17874235

"What" and "where" in word reading: ventral coding of written words revealed by parietal atrophy.

PubMed

Vinckier, Fabien; Naccache, Lionel; Papeix, Caroline; Forget, Joaquim; Hahn-Barma, Valerie; Dehaene, Stanislas; Cohen, Laurent

2006-12-01

The visual system of literate adults develops a remarkable perceptual expertise for printed words. To delineate the aspects of this competence intrinsic to the occipitotemporal "what" pathway, we studied a patient with bilateral lesions of the occipitoparietal "where" pathway. Depending on critical geometric features of the display (rotation angle, letter spacing, mirror reversal, etc.), she switched from a good performance, when her intact ventral pathway was sufficient to encode words, to severely impaired reading, when her parietal lesions prevented the use of alternative reading strategies as a result of spatial and attentional impairments. In particular, reading was disrupted (a) by rotating word by more than 50 degrees , providing an approximation of the invariance range for words encoding in the ventral pathway; (b) by separating letters with double spaces, revealing the limits of letter grouping into perceptual wholes; (c) by mirror-reversing words, showing that words escape the default mirror-invariant representation of visual objects in the ventral pathway. Moreover, because of her parietal lesions, she was unable to discriminate mirror images of common objects, although she was excellent with reversible pseudowords, confirming that the breaking of mirror symmetry was intrinsic to the occipitotemporal cortex. Thus, charting the display conditions associated with preserved or impaired performance allowed us to infer properties of word coding in the normal ventral pathway and to delineate the roles of the parietal lobes in single-word recognition.

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

PubMed

Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

2017-05-01

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

PubMed

Mitchell, D G V; Fine, C; Richell, R A; Newman, C; Lumsden, J; Blair, K S; Blair, R J R

2006-05-01

Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. Copyright (c) 2006 APA, all rights reserved.

Involvement of HLA class I molecules in the immune escape of urologic tumors.

PubMed

Carretero, R; Gil-Julio, H; Vázquez-Alonso, F; Garrido, F; Castiñeiras, J; Cózar, J M

2014-04-01

To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Agraphia of the left hand with dysfunction of the left superior parietal region without callosal lesions.

PubMed

Kinno, Ryuta; Ohashi, Hideaki; Mori, Yukiko; Shiromaru, Azusa; Ono, Kenjiro

2018-03-01

A 28-year-old right-handed man noticed weakness in his legs, three days after an ephedrine overdose. Initial brain magnetic resonance imaging showed lesions in the parietal regions bilaterally. Computed tomography angiography showed segmental and multifocal vasoconstriction of the cerebral arteries. After treatment, clinical and radiological findings resolved, suggesting the patient had reversible cerebral vasoconstriction syndrome with posterior reversible encephalopathy syndrome. However, he had residual agraphia of the left hand. Language testing revealed no difficulties in oral expression, auditory comprehension, understanding of written language, or writing with the right hand. I-123 iodoamphetamine single-photon emission computed tomography showed residual dysfunction in the left superior parietal lobule. There were no apparent signs of other disconnection syndromes or neuroimaging abnormalities in the corpus callosum. We diagnosed left-hand agraphia due to left parietal dysfunction. Our case suggests that left superior parietal dysfunction without callosal lesions is a possible cause of left-hand agraphia. Neural mechanisms for writing with the right or left hand may be separable at the cortical level.

Impaired threat prioritisation after selective bilateral amygdala lesions

PubMed Central

Bach, Dominik R.; Hurlemann, Rene; Dolan, Raymond J.

2015-01-01

The amygdala is proposed to process threat-related information in non-human animals. In humans, empirical evidence from lesion studies has provided the strongest evidence for a role in emotional face recognition and social judgement. Here we use a face-in-the-crowd (FITC) task which in healthy control individuals reveals prioritised threat processing, evident in faster serial search for angry compared to happy target faces. We investigate AM and BG, two individuals with bilateral amygdala lesions due to Urbach–Wiethe syndrome, and 16 control individuals. In lesion patients we show a reversal of a threat detection advantage indicating a profound impairment in prioritising threat information. This is the first direct demonstration that human amygdala lesions impair prioritisation of threatening faces, providing evidence that this structure has a causal role in responding to imminent danger. PMID:25282058

Simultaneous Detection of Rift Valley Fever, Bluetongue, Rinderpest, and Peste des Petits Ruminants Viruses by a Single-Tube Multiplex Reverse Transcriptase-PCR Assay Using a Dual-Priming Oligonucleotide System▿

PubMed Central

Yeh, Jung-Yong; Lee, Ji-Hye; Seo, Hyun-Ji; Park, Jee-Yong; Moon, Jin-San; Cho, In-Soo; Choi, In-Soo; Park, Seung-Yong; Song, Chang-Seon; Lee, Joong-Bok

2011-01-01

The aim of this study was to develop a highly sensitive and specific one-step multiplex reverse transcriptase PCR assay for the simultaneous and differential detection of Rift Valley Fever virus (RVFV), bluetongue virus (BTV), rinderpest virus (RPV), and Peste des petits ruminants virus (PPRV). These viruses cause mucosal lesions in cattle, sheep, and goats, and they are difficult to differentiate from one another based solely on their clinical presentation in suspected disease cases. In this study, we developed a multiplex reverse transcriptase PCR to detect these viruses using a novel dual-priming oligonucleotide (DPO). The DPO contains two separate priming regions joined by a polydeoxyinosine linker, which blocks extension of nonspecifically primed templates and consistently allows high PCR specificity even under less-than-optimal PCR conditions. A total of 19 DPO primers were designed to detect and discriminate between RVFV, BTV, RPV, and PPRV by the generation of 205-, 440-, 115-, and 243-bp cDNA products, respectively. The multiplex reverse transcriptase PCR described here enables the early diagnosis of these four viruses and may also be useful as part of a testing regime for cattle, sheep, or goats exhibiting similar clinical signs, including mucosal lesions. PMID:21307219

Functional and cellular responses to laser injury in the rat snake retina

NASA Astrophysics Data System (ADS)

Glickman, Randolph D.; Elliott, W. Rowe, III; Kumar, Neeru

2007-02-01

Acute (1-hr, 6-hr) and longer term (24-hr) effects of laser injury on retinal function and cellular responses have been studied in the Great Plains rat snake, Elaphe guttata emoryi. This animal is of interest for vision research because its eye has an all-cone retina. A linear array of 5 thermal lesions was placed in the retina of anesthetized animals, near the area centralis, using a Nd:VO 4 laser (532 nm), that delivered 50 mW per 10-msec pulse. Retinal function was assessed with the pattern electroretinogram (PERG), recorded before and after the placement of the lesions. PERGs were elicited with counterphased square-wave gratings, and were analyzed by Fourier analysis. The fate of lesioned cells was assessed by immunohistological staining for the transcription factor, NF-κB (which is activated by ionizing and nonionizing radiation), as well as for the apoptosis marker, caspase-9. The normal snake PERG had the maximum, real amplitude frequency component, determined by Fourier analysis, at the reversal frequency of the grating (i.e. shifts/sec). In the hour following the lesion-producing laser exposures, the PERG response exhibited frequency doubling, i.e. a new response waveform appeared at twice the reversal frequency. By 24-hr post exposure, many lesioned photoreceptors stained positively for both NF-κB and caspase 9. Because the PERG largely reflects retinal ganglion cell activity, the appearance of frequency doubling in the PERG suggests that complementary (push-pull) inputs to ganglion cells are disrupted by the laser lesions. The immunohistological results indicate that activation of NF- B is not necessarily associated with photoreceptor survival after a laser injury.

[A case of migraine presenting with thunderclap headache associated with posterior reversible encephalopathy syndrome].

PubMed

Katoh, Hirotaka; Saito, Yu; Ohwan, Yoshiyuki; Kasai, Hideyo; Fujita, Kazuhisa; Kawamura, Mitsuru

2014-10-01

We report a 47-year-old woman who developed a thunderclap headache. Head axial, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) revealed high signal lesions in the left occipital and right parietal lobes. Apparent diffusion coefficient mapping showed a vasogenic edema pattern. Upon admission, the patient's blood pressure was normal and the neurological examination was unremarkable. As thunderclap headaches are associated with a repeated rise in blood pressure, we considered cerebral vasoconstriction and administered a calcium channel blocker. Thereafter, her headache with high blood pressure eased significantly and the high signal lesions on FLAIR MRI disappeared. We diagnosed the condition as posterior reversible encephalopathy syndrome (PRES). In addition, head magnetic resonance angiogram showed vasoconstriction of the right anterior cerebral artery, left middle cerebral artery, and bilateral posterior cerebral artery. Calcium channel blocker use was continued and vasoconstriction improved by day 70. In this case, the presenting symptom was thunderclap headache, which is a characteristic feature of reversible cerebral vasoconstriction syndrome (RCVS). Therefore, PRES may be caused by RCVS.

Time reversal for ultrasonic transcranial surgery and echographic imaging

NASA Astrophysics Data System (ADS)

Tanter, Mickael; Aubry, Jean-Francois; Vignon, Francois; Fink, Mathias

2005-09-01

High-intensity focused ultrasound (HIFU) is able to induce non-invasively controlled and selective destruction of tissues by focusing ultrasonic beams within organs, analogous to a magnifying glass that concentrates enough sunlight to burn a hole in paper. The brain is an attractive organ in which to perform ultrasonic tissue ablation, but such an application has been hampered by the strong defocusing effect of the skull bone. Our group has been involved in this topic for several years, providing proofs of concept and proposing technological solutions to this problem. Thanks to a high-power time-reversal mirror, presented here are in vivo thermal lesions induced through the skull of 12 sheep. Thermal lesions were confirmed by T2-weighted magnetic resonance post-treatment images and histological examination. These results provide striking evidence that noninvasive ultrasound brain surgery is feasible. A recent approach for high-resolution brain ultrasonic imaging will also be discussed with a skull aberration correction technique based on twin arrays technology. The correction of transcranial ultrasonic images is implemented on a new generation of time-reversal mirrors relying on a fully programmable transmit and receive beamformer.

Glenohumeral instability: evaluation with MR arthrography.

PubMed

Beltran, J; Rosenberg, Z S; Chandnani, V P; Cuomo, F; Beltran, S; Rokito, A

1997-01-01

Magnetic resonance arthrography is superior to other imaging techniques in evaluation of the glenohumeral joint. Normal variants that can be diagnostic pitfalls include the anterosuperior sublabral foramen, the Buford complex, and hyaline cartilage under the labrum. Anteroinferior dislocation is the most frequent cause of anterior glenohumeral instability and produces a constellation of lesions (anteroinferior labral tear, classic and osseous Bankart lesions, Hill-Sachs lesion). Variants of anteroinferior labral tears include anterior labroligamentous periosteal sleeve avulsion and glenoid labral articular disruption. Anterior glenohumeral instability can also involve tears of the anterior or anterosuperior labrum or the glenohumeral ligaments. Posterior glenohumeral instability can involve a posterior labral tear, posterior capsular stripping or laxity; fracture, erosion, or sclerosis and ectopic ossification of the posterior glenoid fossa; reverse Hill-Sachs lesion; McLaughlin fracture; or posterosuperior glenoid impingement. Superior labral anterior and posterior lesions involve the superior labrum with varying degrees of biceps tendon involvement.

Push back to respond better: regulatory inhibition of the DNA double-strand break response.

PubMed

Panier, Stephanie; Durocher, Daniel

2013-10-01

Single DNA lesions such as DNA double-strand breaks (DSBs) can cause cell death or trigger genome rearrangements that have oncogenic potential, and so the pathways that mend and signal DNA damage must be highly sensitive but, at the same time, selective and reversible. When initiated, boundaries must be set to restrict the DSB response to the site of the lesion. The integration of positive and, crucially, negative control points involving post-translational modifications such as phosphorylation, ubiquitylation and acetylation is key for building fast, effective responses to DNA damage and for mitigating the impact of DNA lesions on genome integrity.

Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study.

PubMed

Wu, Yupeng; Sun, Dandan; Wang, Yong; Wang, Yibao; Ou, Shaowu

2016-01-01

The cingulum bundle (CB) is a critical white matter fiber tract in the brain, which forms connections between the frontal lobe, parietal lobe and temporal lobe. In non-human primates, the CB is actually divided into distinct subcomponents on the basis of corticocortical connections. However, at present, no study has verified similar distinct subdivisions in the human brain. In this study, we reconstructed these distinct subdivisions in the human brain, and determined their exact cortical connections using high definition fiber tracking (HDFT) technique on 10 healthy adults and a 488-subject template from the Human Connectome Project (HCP-488). Fiber dissections were performed to verify tractography results. Five CB segments were identified. CB-I ran from the subrostral areas to the precuneus and splenium, encircling the corpus callosum (CC). CB-II arched around the splenium and extended anteriorly above the CC to the medial aspect of the superior frontal gyrus (SFG). CB-III connected the superior parietal lobule (SPL) and precuneus with the medial aspect of the SFG. CB-IV was a relatively minor subcomponent from the SPL and precuneus to the frontal region. CB-V, the para-hippocampal cingulum, stemmed from the medial temporal lobe and fanned out to the occipital lobes. Our findings not only provide a more accurate and detailed description on the associated architecture of the subcomponents within the CB, but also offer new insights into the functional role of the CB in the human brain.

Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex.

PubMed

Kirsch, V; Keeser, D; Hergenroeder, T; Erat, O; Ertl-Wagner, B; Brandt, T; Dieterich, M

2016-04-01

Structural and functional interconnections of the bilateral central vestibular network have not yet been completely delineated. This includes both ipsilateral and contralateral pathways and crossing sites on the way from the vestibular nuclei via the thalamic relay stations to multiple "vestibular cortex" areas. This study investigated "vestibular" connectivity in the living human brain in between the vestibular nuclei and the parieto-insular vestibular cortex (PIVC) by combined structural and functional connectivity mapping using diffusion tensor imaging and functional connectivity magnetic resonance imaging in 24 healthy right-handed volunteers. We observed a congruent functional and structural link between the vestibular nuclei and the ipsilateral and contralateral PIVC. Five separate and distinct vestibular pathways were identified: three run ipsilaterally, while the two others cross either in the pons or the midbrain. Two of the ipsilateral projections run through the posterolateral or paramedian thalamic subnuclei, while the third bypasses the thalamus to reach the inferior part of the insular cortex directly. Both contralateral pathways travel through the posterolateral thalamus. At the cortical level, the PIVC regions of both hemispheres with a right hemispherical dominance are interconnected transcallosally through the antero-caudal splenium. The above-described bilateral vestibular circuitry in its entirety takes the form of a structure of a rope ladder extending from the brainstem to the cortex with three crossings in the brainstem (vestibular nuclei, pons, midbrain), none at thalamic level and a fourth cortical crossing through the splenium of the corpus callosum.

Fragile X-associated tremor/ataxia syndrome: An under-recognised cause of tremor and ataxia.

PubMed

Kalus, Sarah; King, John; Lui, Elaine; Gaillard, Frank

2016-01-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive degenerative movement disorder resulting from a fragile X "premutation", defined as 55-200 CGG repeats in the 5'-untranslated region of the FMR1 gene. The FMR1 premutation occurs in 1/800 males and 1/250 females, with FXTAS affecting 40-45% of male and 8-16% of female premutation carriers over the age of 50. FXTAS typically presents with kinetic tremor and cerebellar ataxia. FXTAS has a classical imaging profile which, in concert with clinical manifestations and genetic testing, participates vitally in its diagnosis. The revised FXTAS diagnostic criteria include two major radiological features. The "MCP sign", referring to T2 hyperintensity in the middle cerebellar peduncle, has long been considered the radiological hallmark of FXTAS. Recently included as a major radiological criterion in the diagnosis of FXTAS is T2 hyperintensity in the splenium of the corpus callosum. Other imaging features of FXTAS include T2 hyperintensities in the pons, insula and periventricular white matter as well as generalised brain and cerebellar atrophy. FXTAS is an under-recognised and misdiagnosed entity. In patients with unexplained tremor, ataxia and cognitive decline, the presence of middle cerebellar peduncle and/or corpus callosum splenium hyperintensity should raise suspicion of FXTAS. Diagnosis of FXTAS has important implications not only for the patient but also, through genetic counselling and testing, for future generations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormal brain connectivity in first-episode psychosis: A diffusion MRI tractography study of the corpus callosum

PubMed Central

Price, Gary; Cercignani, Mara; Parker, Geoffrey J.M.; Altmann, Daniel R.; Barnes, Thomas R.E.; Barker, Gareth J.; Joyce, Eileen M.; Ron, Maria A.

2007-01-01

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the clinical manifestations of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail and we present here a study of patients with first-episode psychosis using this technique. We selected the corpus callosum for this study because there is evidence that it is abnormal in schizophrenia. In addition, the topographical organization of its fibers makes it possible to relate focal abnormalities to specific cortical regions. Eighteen patients with first-episode psychosis and 21 healthy subjects took part in the study. A probabilistic tractography algorithm (PICo) was used to study fractional anisotropy (FA). Seed regions were placed in the genu and splenium to track fiber tracts traversing these regions, and a multi-threshold approach to study the probability of connection was used. Multiple linear regressions were used to explore group differences. FA, a measure of tract coherence, was reduced in tracts crossing the genu, and to a lesser degree the splenium, in patients compared with controls. FA was also lower in the genu in females across both groups, but there was no gender-by-group interaction. The FA reduction in patients may be due to aberrant myelination or axonal abnormalities, but the similar tract volumes in the two groups suggest that severe axonal loss is unlikely at this stage of the illness. PMID:17275337

New subtraction algorithms for evaluation of lesions on dynamic contrast-enhanced MR mammography.

PubMed

Choi, Byung Gil; Kim, Hak Hee; Kim, Euy Neyng; Kim, Bum-soo; Han, Ji-Youn; Yoo, Seung-Schik; Park, Seog Hee

2002-12-01

We report new subtraction algorithms for the detection of lesions in dynamic contrast-enhanced MR mammography(CE MRM). Twenty-five patients with suspicious breast lesions underwent dynamic CE MRM using 3D fast low-angle shot. After the acquisition of the T1-weighted scout images, dynamic images were acquired six times after the bolus injection of contrast media. Serial subtractions, step-by-step subtractions, and reverse subtractions, were performed. Two radiologists attempted to differentiate benign from malignant lesion in consensus. The sensitivity, specificity, and accuracy of the method leading to the differentiation of malignant tumor from benign lesions were 85.7, 100, and 96%, respectively. Subtraction images allowed for better visualization of the enhancement as well as its temporal pattern than visual inspection of dynamic images alone. Our findings suggest that the new subtraction algorithm is adequate for screening malignant breast lesions and can potentially replace the time-intensity profile analysis on user-selected regions of interest.

Expression of IL-33 in chronic lesional skin of canine atopic dermatitis.

PubMed

Asahina, Ryota; Nishida, Hidetaka; Kamishina, Hiroaki; Maeda, Sadatoshi

2018-06-01

In humans, interleukin (IL)-33 plays a critical role in the enhancement of allergic skin inflammation. However, it currently remains unclear whether IL-33 is involved in the pathogenesis of canine atopic dermatitis (cAD). To examine the expression of IL-33 in chronic lesional skin of cAD. Eight dogs with spontaneous cAD and five healthy dogs were used. The transcription of il-33 in chronic lesional skin of cAD was quantified by quantitative reverse transcription PCR. The expression of IL-33 was evaluated immunohistochemically using an anti-human IL-33 monoclonal antibody with cross-reactivity to canine IL-33. The transcription levels of il-33 in chronic lesional skin of cAD were significantly higher than those in normal skin of healthy dogs. Keratinocytes were a major cellular source of IL-33 production in chronic lesional skin of cAD. The results indicate that IL-33 is involved in chronic lesional skin of cAD. © 2018 ESVD and ACVD.

A prospective study of diffusion weighted magnetic resonance imaging abnormalities in patients with cluster of seizures and status epilepticus.

PubMed

Jabeen, S A; Cherukuri, Pavankumar; Mridula, Rukmini; Harshavardhana, K R; Gaddamanugu, Padmaja; Sarva, Sailaja; Meena, A K; Borgohain, Rupam; Jyotsna Rani, Y

2017-04-01

To study the frequency, imaging characteristics, and clinical predictors for development of periictal diffusion weighted MRI abnormalities. We prospectively analyzed electro clinical and imaging characteristic of adult patients with cluster of seizures or status epilepticus between November 2013 and November 2015, in whom the diffusion weighted imaging was done within 24h after the end of last seizure (clinical or electrographic). There were thirty patients who fulfilled the inclusion and exclusion criteria. Twenty patients (66%) had periictal MRI abnormalities. Nine patients (34%) did not have any MRI abnormality. All the patients with PMA had abnormalities on diffusion weighted imaging (DWI). Hippocampal abnormalities were seen in nine (53%), perisylvian in two (11.7%), thalamic in five (30%), splenium involvement in two (11.7%) and cortical involvement (temporo-occipital, parieto-occipital, temporo-parietal, fronto-parietal and fronto-temporal) in sixteen (94.1%) patients. Complete reversal of DWI changes was noted in sixteen (80%) patients and four (20%) patients showed partial resolution of MRI abnormalities. Mean duration of seizures was significantly higher among patients with PMA (59.11+20.97h) compared to those without MRI changes (27.33+9.33h) (p<0.001). Diffusion abnormalities on MRI are common in patients with cluster of seizures and status epilepticus and were highly concordant with clinical semiology and EEG activity. Patients with longer duration of seizures/status were more likely to have PMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison between histopathologic features of leprosy in reaction lesions in HIV coinfected and non-coinfected patients.

PubMed

Pires, Carla Andréa Avelar; Miranda, Mario Fernando Ribeiro de; Bittencourt, Maraya de Jesus Semblano; Brito, Arival Cardoso de; Xavier, Marília Brasil

2015-01-01

Leprosy and HIV are diseases that have a major impact on public health in Brazil. Patients coinfected with both diseases, appear to be at higher risk to develop leprosy reactions. The aim of this study is to describe the histopathological aspects of cutaneous lesions during reactional states in a group of patients with HIV-leprosy coinfection, compared to patients with leprosy, without coinfection. Two groups were established: group 1 comprised of 40 patients coinfected with HIV-leprosy; group 2, comprised of 107 patients with leprosy only. Patients presenting reactional states of leprosy had their lesions biopsied and comparatively evaluated. Reversal reaction was the most frequent feature in both groups, with dermis edema as the most common histopathological finding. Giant cells were seen in all group 1 histopathological examinations. Dermis edema was the most common finding in patients with erythema nodosum leprosum. Few histopathological differences were found in both groups, with reversal reaction as the most significant one, although this fact should be analyzed considering the predominant BT clinical form in the coinfected group and BB form in the group without HIV. Larger prospective studies in patients with HIV-leprosy coinfection are needed to confirm and broaden these results.

Color vision abnormality as the sole manifestation of posterior reversible encephalopathy due to post-partum HELLP syndrome.

PubMed

Takahashi, Hironori; Matsubara, Teppei; Makino, Shinji; Horie, Kenji; Matsubara, Shigeki

2017-03-01

Posterior reversible encephalopathy syndrome (PRES) is associated with several symptoms; of those, visual acuity loss, light oversensitivity (photophobia), and light flashes (photopsia) are known as PRES-related eye symptoms. We report a post-partum woman with PRES associated with hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP), in whom color vision abnormality (achromatopsia) was the sole manifestation. Cesarean section was performed at 28 weeks due to headache, epigastralgia, and severe hypertension. HELLP became evident after delivery. On post-partum day 1, she complained of achromatopsia, stating: "all things look brownish-gray". Ophthalmologic examination was normal, but brain magnetic resonance imaging showed occipital lobe lesions, indicative of PRES, and, interestingly, also color vision center (area V4) lesions, suggesting that the achromatopsia had been caused by brain damage. It may be prudent to question HELLP patients concerning achromatopsia. © 2017 Japan Society of Obstetrics and Gynecology.

[Reversible neurotoxicity secondary to metronidazole: report of one case].

PubMed

Retamal-Riquelme, Eva; Soto-San Martín, Hernán; Vallejos-Castro, José; Galdames-Poblete, Daniel

2014-03-01

Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

Spectrum of magnetic resonance imaging findings in clinical glenohumeral instability

PubMed Central

Jana, Manisha; Srivastava, Deep Narayan; Sharma, Raju; Gamanagatti, Shivanand; Nag, Hiralal; Mittal, Ravi; Upadhyay, Ashish Dutt

2011-01-01

The glenohumeral joint is the most commonly dislocated joint in the body, and anterior instability is the most common type of shoulder instability. Depending on the etiology and the age of the patient, there may be associated injuries, for example, to the anterior-inferior labro-ligamentous structures (in young individuals with traumatic instability) or to the bony components (commoner in the elderly), which are best visualized using MRI and MR arthrography. Anterior instability is associated with a Bankart lesion and its variants and abnormalities of the anterior band of the inferior glenohumeral ligament (IGHL), whereas posterior instability is associated with reverse Bankart and reverse Hill-Sachs lesions. Cases of multidirectional instability often have no labral pathology on imaging but show specific osseous changes including increased chondrolabral retroversion. This article reviews the relevant anatomy in brief and describes the MRI findings in each type, with the imaging features of the common abnormalities. PMID:21799591

Brain White Matter Tract Integrity and Cognitive Abilities in Community-Dwelling Older People: The Lothian Birth Cohort, 1936

PubMed Central

2013-01-01

Objective: The present study investigates associations between brain white matter tract integrity and cognitive abilities in community-dwelling older people (N = 655). We explored two potential confounds of white matter tract−cognition associations in later life: (a) whether the associations between tracts and specific cognitive abilities are accounted for by general cognitive ability (g); and (b) how the presence of atrophy and white matter lesions affect these associations. Method: Tract integrity was determined using quantitative diffusion magnetic resonance imaging tractography (tract-averaged fractional anisotropy [FA]). Using confirmatory factor analysis, we compared first-order and bifactor models to investigate whether specific tract-ability associations were accounted for by g. Results: Significant associations were found between g and FA in bilateral anterior thalamic radiations (r range: .16−.18, p < .01), uncinate (r range: .19−.26, p < .001), arcuate fasciculi (r range: .11−.12, p < .05), and the splenium of corpus callosum (r = .14, p < .01). After controlling for g within the bifactor model, some significant specific cognitive domain associations remained. Results also suggest that the primary effects of controlling for whole brain integrity were on g associations, not specific abilities. Conclusion: Results suggest that g accounts for most of, but not all, the tract−cognition associations in the current data. When controlling for age-related overall brain structural changes, only minor attenuations of the tract−cognition associations were found, and these were primarily with g. In totality, the results highlight the importance of controlling for g when investigating associations between specific cognitive abilities and neuropsychology variables. PMID:23937481

Effect of l-DOPA on local field potential relationship between the pedunculopontine nucleus and primary motor cortex in a rat model of Parkinson's disease.

PubMed

Geng, Xiwen; Wang, Xuenan; Xie, Jinlu; Zhang, Xiao; Wang, Xiusong; Hou, Yabing; Lei, Chengdong; Li, Min; Han, Hongyu; Yao, Xiaomeng; Zhang, Qun; Wang, Min

2016-12-15

Levodopa (l-DOPA) has been proved to reverse the pathologic neuron activities in many brain regions related to Parkinson's disease (PD). But little is known about the effect of l-DOPA on the altered electrophysiological coherent activities between pedunculopontine nucleus (PPN) and motor cortex. To investigate this, local field potentials (LFPs) of PPN and primary motor cortex (M1) were recorded simultaneously in control, 6-hydroxydopamine lesioned and lesioned rats with l-DOPA chronic treatment. The results revealed that in resting state, chronic l-DOPA treatment could correct the suppressed power of LFPs in PPN and M1 in low-frequency band (1-7Hz) and the enhanced power in high-frequency band (7-70Hz in PPN and 12-70Hz in M1) of lesioned rats. In locomotor state, l-DOPA treatment could correct the alterations in most of frequency bands except the δ band in PPN and α band in M1. Moreover, l-DOPA could also reverse the altered coherent relationships caused by dopamine depletion in resting state between PPN and M1 in β band. And in locomotor state, l-DOPA had therapeutic effect on the alterations in δ and β bands but not in the α band. These findings provide evidence that l-DOPA can reverse the altered LFP activities in PPN and M1 and their relationships in a rat model of PD, which contributes to better understanding the electrophysiological mechanisms of the pathophysiology and therapy of PD. Copyright © 2016. Published by Elsevier B.V.

Reversion of 6-thioguanine resistant Chinese hamster cell lines: agent specificity and evidence for the repair of promutagenic lesions.

PubMed

Hodgkiss, R J; Brennand, J; Fox, M

1980-02-01

The kinetics and mutagen specificity of reversion of an HGPRT(-)TG(R) line of Chinese hamster cells have been examined in detail by measuring the frequency of HAT(R) colonies. Alkylating agents which produce relatively high levels of O-atom reaction were effective in inducing reversion. MMS, DMS and u.v. were less efficient, and aflatoxin B1, acridine orange and N-acetoxy-AAF were completely ineffective. For agents which were effective, the relationship between HAT(R) colony frequency and dose of mutagen was linear at early expression times (6 h). HAT(R) colony frequency fell subsequently at all doses and the rate and extent of the fall was inversely related to dose. These observations suggest repair of a pro-mutagenic DNA lesion. Other TG(R) mutants isolated from the same wild-type cell line under different selective conditions were also tested for revertibility after exposure to the same mutagens. The majority did not revert, this suggests that they carry deletions within the structural gene for HGPRT. The infrequent revertible lines all arose spontaneously and our evidence suggests that they carry nonsense mutations.

Depression- and anxiety-like behaviour is related to BDNF/TrkB signalling in a mouse model of psoriasis.

PubMed

JiaWen, W; Hong, S; ShengXiang, X; Jing, L

2018-04-01

The prevalence of anxiety and depression is significantly higher in individuals with psoriasis than in the general population. Clinical data also show that anti-anxiety and antidepression drugs can reduce skin lesions in patients with psoriasis, but the actual mechanism is still poorly understood. To investigate whether brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB) signalling plays a role in the mechanism underlying psoriasis with depression and anxiety behaviours. Expression of BDNF and tropomyosin receptor kinase B (TrKB) in the K5.Stat3C mouse, an animal model of psoriasis, were investigated by reverse transcription PCR and Western blotting. Anxiety-like behaviours in the elevated-plus maze test and changes in BDNF/TrkB that have been implicated in depression and anxiety behaviours were measured. Skin lesions induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) were also measured when the mice were administered fluoxetine and K252a, an antagonist of TrkB. The antidepression and anti-anxiety drug fluoxetine reduced TPA-induced skin lesions and increased expression of BDNF and TrkB in K5.Stat3C mice. More importantly, the effects of fluoxetine were reversed by the TrkB antagonist K252a. BDNF/TrkB signalling participates in the pathological mechanism of depression and anxiety behaviours in psoriasis. Our findings provide a new therapeutic strategy for the treatment of skin lesions in psoriasis. © 2018 British Association of Dermatologists.

A combined endovascular and open ''reverse hybrid'' technique for repair of complex juxtarenal inflammatory aortic aneurysms.

PubMed

Rigberg, David; Jimenez, Juan Carlos; Lawrence, Peter; Gelabert, Hugh

2009-01-01

Inflammatory abdominal aortic aneurysms (IAAA) can present significant challenges to surgeons, especially in the juxtarenal location where they may not be amenable to endovascular repair. The dense, inflammatory component of these lesions can encase adjacent structures including the duodenum, ureters, and inferior vena cava putting them at risk for injury during open exposure. We report a novel ''reverse hybrid'' technique using a combined endovascular and open approach for repair of large, juxtarenal IAAA's.

Electrolytic lesions of the bilateral ventrolateral orbital cortex inhibit methamphetamine-associated contextual memory formation in rats.

PubMed

Zhao, Yan; Liu, Peng; Chu, Zheng; Liu, Fei; Han, Wei; Xun, Xi; Dang, Yong-Hui

2015-10-22

The memories that are formed between rewarding and drug-associated contextual cues have been suggested to contribute to drug addiction relapse. Recent evidence has indicated that the ventrolateral orbital cortex (VLO) plays important roles in reward-based learning and reversal learning. However, whether the VLO is required for methamphetamine-induced contextual memory formation is not well understood. In the present study, a three-phase methamphetamine-induced conditioned place preference (CPP) model was used to investigate the effects of VLO lesions on the formation of drug-associated contextual memories in rats. We found that the VLO lesions themselves elicited no observable effects on place preferences. However, the VLO lesions delayed the acquisition and extinction phases of CPP without affecting the expression level. Furthermore, the VLO lesions did not have an obvious influence on CPP reinstatement. These results indicate that electrolytic lesions of the bilateral ventrolateral orbital cortex can inhibit the formation of methamphetamine-induced contextual memories in rats. Moreover, VLO may not be critically involved in memory storage and retrieval. Copyright © 2015 Elsevier B.V. All rights reserved.

Relationship between human cytomegalovirus transcription and symptomatic apical periodontitis in Iran.

PubMed

Yazdi, K A; Sabeti, M; Jabalameli, F; Eman eini, M; Kolahdouzan, S A; Slots, J

2008-12-01

Apical periodontitis of endodontic origin may develop as a result of cooperative interactions among herpesviruses, specific pathogenic bacteria and tissue-destructive inflammatory mediators. This study sought to identify the presence of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) transcripts in symptomatic and asymptomatic periapical lesions of individuals living in Iran. Fifty endodontic patients (28 with symptomatic periapical lesions and 22 with asymptomatic periapical lesions) were included in the study. In each study subject, a microbiological periapical sample was collected using a curette in conjunction with periapical surgery. A reverse transcription-polymerase chain reaction assay was used to identify transcripts of EBV and HCMV. Human cytomegalovirus transcript was detected in 15 of the 28 (53.6%) symptomatic and in six of the 22 (27.3%) asymptomatic periapical study lesions (significant difference between symptomatic and asymptomatic lesions; P = 0.03, chi-square test). Epstein-Barr virus transcript was identified in one symptomatic and in two asymptomatic periapical lesions. This study establishes that HCMV transcription is common in apical periodontitis and is most frequent in symptomatic lesions. The high frequency of active herpesvirus infections in severe apical periodontitis changes the pathogenic paradigm of the disease and may also have preventive and therapeutic implications.

Effect of registration on corpus callosum population differences found with DBM analysis

NASA Astrophysics Data System (ADS)

Han, Zhaoying; Thornton-Wells, Tricia A.; Gore, John C.; Dawant, Benoit M.

2011-03-01

Deformation Based Morphometry (DBM) is a relatively new method used for characterizing anatomical differences among populations. DBM is based on the analysis of the deformation fields generated by non-rigid registration algorithms, which warp the individual volumes to one standard coordinate system. Although several studies have compared non-rigid registration algorithms for segmentation tasks, few studies have compared the effect of the registration algorithm on population differences that may be uncovered through DBM. In this study, we compared DBM results obtained with five well established non-rigid registration algorithms on the corpus callosum (CC) in thirteen subjects with Williams Syndrome (WS) and thirteen Normal Control (NC) subjects. The five non-rigid registration algorithms include: (1) The Adaptive Basis Algorithm (ABA); (2) Image Registration Toolkit (IRTK); (3) FSL Nonlinear Image Registration Tool (FSL); (4) Automatic Registration Tools (ART); and (5) the normalization algorithm available in SPM8. For each algorithm, the 3D deformation fields from all subjects to the atlas were obtained and used to calculate the Jacobian determinant (JAC) at each voxel in the mid-sagittal slice of the CC. The mean JAC maps for each group were compared quantitatively across different nonrigid registration algorithms. An ANOVA test performed on the means of the JAC over the Genu and the Splenium ROIs shows the JAC differences between nonrigid registration algorithms are statistically significant over the Genu for both groups and over the Splenium for the NC group. These results suggest that it is important to consider the effect of registration when using DBM to compute morphological differences in populations.

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults

PubMed Central

Paul, Robert H.; Grieve, Stuart M.; Niaura, Raymond; David, Sean P.; Laidlaw, David H.; Cohen, Ronald; Sweet, Lawrence; Taylor, George; Clark, C. Richard; Pogun, Sakire; Gordon, Evian

2008-01-01

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers. PMID:18188754

Structural changes of the corpus callosum in tinnitus

PubMed Central

Diesch, Eugen; Schummer, Verena; Kramer, Martin; Rupp, Andre

2012-01-01

Objectives: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. Methods: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). Results: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. Conclusion: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres. PMID:22470322

Anterior interhemispheric transsplenial approach to pineal region tumors: anatomical study and illustrative case.

PubMed

Yağmurlu, Kaan; Zaidi, Hasan A; Kalani, M Yashar S; Rhoton, Albert L; Preul, Mark C; Spetzler, Robert F

2018-01-01

Pineal region tumors are challenging to access because they are centrally located within the calvaria and surrounded by critical neurovascular structures. The goal of this work is to describe a new surgical trajectory, the anterior interhemispheric transsplenial approach, to the pineal region and falcotentorial junction area. To demonstrate this approach, the authors examined 7 adult formalin-fixed silicone-injected cadaveric heads and 2 fresh human brain specimens. One representative case of falcotentorial meningioma treated through an anterior interhemispheric transsplenial approach is also described. Among the interhemispheric approaches to the pineal region, the anterior interhemispheric transsplenial approach has several advantages. 1) There are few or no bridging veins at the level of the pericoronal suture. 2) The parietal and occipital lobes are not retracted, which reduces the chances of approach-related morbidity, especially in the dominant hemisphere. 3) The risk of damage to the deep venous structures is low because the tumor surface reached first is relatively vein free. 4) The internal cerebral veins can be manipulated and dissected away laterally through the anterior interhemispheric route but not via the posterior interhemispheric route. 5) Early control of medial posterior choroidal arteries is obtained. The anterior interhemispheric transsplenial approach provides a safe and effective surgical corridor for patients with supratentorial pineal region tumors that 1) extend superiorly, involve the splenium of the corpus callosum, and push the deep venous system in a posterosuperior or an anteroinferior direction; 2) are tentorial and displace the deep venous system inferiorly; or 3) originate from the splenium of the corpus callosum.

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging.

PubMed

Bültmann, Eva; Nägele, Thomas; Lanfermann, Heinrich; Klose, Uwe

2017-01-01

We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Colour break in reverse bicolour daffodils is associated with the presence of Narcissus mosaic virus

PubMed Central

2011-01-01

Background Daffodils (Narcissus pseudonarcissus) are one of the world's most popular ornamentals. They also provide a scientific model for studying the carotenoid pigments responsible for their yellow and orange flower colours. In reverse bicolour daffodils, the yellow flower trumpet fades to white with age. The flowers of this type of daffodil are particularly prone to colour break whereby, upon opening, the yellow colour of the perianth is observed to be 'broken' into patches of white. This colour break symptom is characteristic of potyviral infections in other ornamentals such as tulips whose colour break is due to alterations in the presence of anthocyanins. However, reverse bicolour flowers displaying colour break show no other virus-like symptoms such as leaf mottling or plant stunting, leading some to argue that the carotenoid-based colour breaking in reverse bicolour flowers may not be caused by virus infection. Results Although potyviruses have been reported to cause colour break in other flower species, enzyme-linked-immunoassays with an antibody specific to the potyviral family showed that potyviruses were not responsible for the occurrence of colour break in reverse bicolour daffodils. Colour break in this type of daffodil was clearly associated with the presence of large quantities of rod-shaped viral particles of lengths 502-580 nm in tepals. Sap from flowers displaying colour break caused red necrotic lesions on Gomphrena globosa, suggesting the presence of potexvirus. Red necrotic lesions were not observed in this indicator plant when sap from reverse bicolour flowers not showing colour break was used. The reverse transcriptase polymerase reactions using degenerate primers to carla-, potex- and poty-viruses linked viral RNA with colour break and sequencing of the amplified products indicated that the potexvirus Narcissisus mosaic virus was the predominant virus associated with the occurrence of the colour break. Conclusions High viral counts were associated with the reverse bicolour daffodil flowers that were displaying colour break but otherwise showed no other symptoms of infection. Narcissus mosaic virus was the virus that was clearly linked to the carotenoid-based colour break. PMID:21854646

Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

PubMed Central

Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

2017-01-01

After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

PubMed

Mastropaolo, J; Nadi, N S; Ostrowski, N L; Crawley, J N

1988-12-01

Galanin coexists with acetylcholine in medial septal neurons projecting to the ventral hippocampus, a projection thought to modulate memory functions. Neurochemical lesions of the nucleus basalis-medial septal area in rats impaired choice accuracy on a delayed alternation t-maze task. Acetylcholine (7.5 or 10 micrograms intraventricularly or 1 micrograms micro-injected into the ventral hippocampus) significantly improved performance in the lesioned rats. Atropine (5 mg/kg intraperitoneally or 10 micrograms intraventricularly), but not mecamylamine (3 mg/kg intraperitoneally or 20 micrograms intraventricularly), blocked this action of acetylcholine, suggesting involvement of a muscarinic receptor. Galanin (100-500 ng intraventricularly or 200 ng into the ventral hippocampus) attenuated the ability of acetylcholine to reverse the deficit in working memory in the lesioned rats. The antagonistic interaction between galanin and acetylcholine suggests that endogenous galanin may inhibit cholinergic function in memory processes, particularly in pathologies such as Alzheimer disease that involve degeneration of basal forebrain neurons.

Amygdala and Ventral Striatum Make Distinct Contributions to Reinforcement Learning.

PubMed

Costa, Vincent D; Dal Monte, Olga; Lucas, Daniel R; Murray, Elisabeth A; Averbeck, Bruno B

2016-10-19

Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL, we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with an RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys' choice reaction times, which emphasized a speed-accuracy trade-off that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. Published by Elsevier Inc.

Amygdala and ventral striatum make distinct contributions to reinforcement learning

PubMed Central

Costa, Vincent D.; Monte, Olga Dal; Lucas, Daniel R.; Murray, Elisabeth A.; Averbeck, Bruno B.

2016-01-01

Summary Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with a RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys’ choice reaction times, which emphasized a speed-accuracy tradeoff that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. PMID:27720488

Comparison between histopathologic features of leprosy in reaction lesions in HIV coinfected and non-coinfected patients*

PubMed Central

Pires, Carla Andréa Avelar; de Miranda, Mario Fernando Ribeiro; Bittencourt, Maraya de Jesus Semblano; de Brito, Arival Cardoso; Xavier, Marília Brasil

2015-01-01

BACKGROUND Leprosy and HIV are diseases that have a major impact on public health in Brazil. Patients coinfected with both diseases, appear to be at higher risk to develop leprosy reactions. OBJECTIVE The aim of this study is to describe the histopathological aspects of cutaneous lesions during reactional states in a group of patients with HIV-leprosy coinfection, compared to patients with leprosy, without coinfection. METHODS Two groups were established: group 1 comprised of 40 patients coinfected with HIV-leprosy; group 2, comprised of 107 patients with leprosy only. Patients presenting reactional states of leprosy had their lesions biopsied and comparatively evaluated. RESULTS Reversal reaction was the most frequent feature in both groups, with dermis edema as the most common histopathological finding. Giant cells were seen in all group 1 histopathological examinations. Dermis edema was the most common finding in patients with erythema nodosum leprosum. CONCLUSION Few histopathological differences were found in both groups, with reversal reaction as the most significant one, although this fact should be analyzed considering the predominant BT clinical form in the coinfected group and BB form in the group without HIV. Larger prospective studies in patients with HIV-leprosy coinfection are needed to confirm and broaden these results. PMID:25672296

Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

PubMed

McNay, E C; Gold, P E

1998-05-15

Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in adults-a case report and literature review.

PubMed

Yuan, Junliang; Yang, Shuna; Wang, Shuangkun; Qin, Wei; Yang, Lei; Hu, Wenli

2017-05-25

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinico-radiological entity characterized by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus callosum, sometimes involved the symmetrical white matters. Many cases of child-onset MERS with various causes have been reported. However, adult-onset MERS is relatively rare. The clinical characteristics and pathophysiologiccal mechanisms of adult-onset MERS are not well understood. We reviewed the literature on adult-onset MERS in order to describe the characteristics of MERS in adults and to provide experiences for clinician. We reported a case of adult-onset MERS with acute urinary retension and performed literature search from PubMed and web of science databases to identify other adult-onset MERS reports from Januarary 2004 to March 2016. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then we summarized the clinico-radiological features of adult-onset MERS. Twenty-nine adult-onset MERS cases were reviewed from available literature including the case we have. 86.2% of the cases (25/29) were reported in Asia, especially in Japan. Ages varied between 18 and 59 years old with a 12:17 female-to-male ratio. The major cause was infection by virus or bacteria. Fever and headache were the most common clinical manifestation, and acute urinary retention was observed in 6 patients. All patients recovered completely within a month. Adult-onset MERS is an entity with a broad clinico-radiological spectrum because of the various diseases and conditions. There are similar characteristics between MERS in adults and children, also some differences.

Ionic plasticity and pain: The loss of descending serotonergic fibers after spinal cord injury transforms how GABA affects pain.

PubMed

Huang, Yung-Jen; Grau, James W

2018-05-02

Activation of pain (nociceptive) fibers can sensitize neural circuits within the spinal cord, inducing an increase in excitability (central sensitization) that can foster chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. In adult animals, the co-transporter KCC2 maintains a low intracellular concentration of the anion Cl - . As a result, when the GABA-A receptor is engaged, Cl - flows in the neuron which has a hyperpolarizing (inhibitory) effect. Spinal cord injury (SCI) can down-regulate KCC2 and reverse the flow of Cl - . Under these conditions, engaging the GABA-A receptor can have a depolarizing (excitatory) effect that fosters the development of nociceptive sensitization. The present paper explores how SCI alters GABA function and provides evidence that the loss of descending fibers alters pain transmission to the brain. Prior work has shown that, after SCI, administration of a GABA-A antagonist blocks the development of capsaicin-induced nociceptive sensitization, implying that GABA release plays an essential role. This excitatory effect is linked to serotonergic (5HT) fibers that descend through the dorsolateral funiculus (DLF) and impact spinal function via the 5HT-1A receptor. Supporting this, blocking the 5HT-1A receptor, or lesioning the DLF, emulated the effect of SCI. Conversely, spinal application of a 5HT-1A agonist up-regulated KCC2 and reversed the effect of bicuculline treatment. Finally, lesioning the DLF reversed how a GABA-A antagonist affects a capsaicin-induced aversion in a place conditioning task; in sham operated animals, bicuculline enhanced aversion whereas in DLF-lesioned rats biciculline had an antinociceptive effect. Copyright © 2018 Elsevier Inc. All rights reserved.

Ischemic lesion volume determination on diffusion weighted images vs. apparent diffusion coefficient maps.

PubMed

Bråtane, Bernt Tore; Bastan, Birgul; Fisher, Marc; Bouley, James; Henninger, Nils

2009-07-07

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride (TTC)-derived infarct volumes. TTC-derived infarct volumes were not significantly different from the ADC and DWI-derived lesion volumes at the last imaging time points except for significantly smaller DWI lesions in the pMCAO model (p=0.02). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived lesions on ADC maps than DWI (p<0.05). Following reperfusion, lesion volumes on the ADC maps significantly reduced but no change was observed on DWI. Visually determined lesion volumes on ADC maps and DWI by both investigators correlated significantly with threshold-derived lesion volumes on ADC maps with the former method demonstrating a stronger correlation. There was also a better interrater agreement for ADC map analysis than for DWI analysis. Ischemic lesion determination by ADC was more accurate in final infarct prediction, rater independent, and provided exclusive information on ischemic lesion reversibility.

Nervous System Abnormalities and Legionnaire's Disease.

PubMed

Halperin, John J

2017-03-01

Although patients with Legionnaire's disease frequently develop alterations of consciousness, this is no more frequent than in patients hospitalized with other, equally severe forms of bacterial pneumonia. Legionella meningitis occurs rarely, if ever. Patients with Legionnaire's are susceptible to critical illness polyneuropathy/myopathy, as are other critically ill patients. Legionnaire's patients may develop MRI hyperdensities in the splenium of the corpus callosum, as may other patients with severe infections. Patients with Legionnaire's may be at increased risk of, and rarely develop, immune-mediated multifocal brain (acute disseminated encephalomyelitis) or peripheral nerve disease (Guillain-Barré syndrome). Copyright © 2016 Elsevier Inc. All rights reserved.

Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern.

PubMed

Barrière, Grégory; Frigon, Alain; Leblond, Hugues; Provencher, Janyne; Rossignol, Serge

2010-08-01

The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.

The neuroimaging of Leigh syndrome: case series and review of the literature.

PubMed

Bonfante, Eliana; Koenig, Mary Kay; Adejumo, Rahmat B; Perinjelil, Vinu; Riascos, Roy F

2016-04-01

Leigh syndrome by definition is (1) a neurodegenerative disease with variable symptoms, (2) caused by mitochondrial dysfunction from a hereditary genetic defect and (3) accompanied by bilateral central nervous system lesions. A genetic etiology is confirmed in approximately 50% of patients, with more than 60 identified mutations in the nuclear and mitochondrial genomes. Here we review the clinical features and imaging studies of Leigh syndrome and describe the neuroimaging findings in a cohort of 17 children with genetically confirmed Leigh syndrome. MR findings include lesions in the brainstem in 9 children (53%), basal ganglia in 13 (76%), thalami in 4 (24%) and dentate nuclei in 2 (12%), and global atrophy in 2 (12%). The brainstem lesions were most frequent in the midbrain and medulla oblongata. With follow-up an increased number of lesions from baseline was observed in 7 of 13 children, evolution of the initial lesion was seen in 6, and complete regression of the lesions was seen in 3. No cerebral white matter lesions were found in any of the 17 children. In concordance with the literature, we found that Leigh syndrome follows a similar pattern of bilateral, symmetrical basal ganglia or brainstem changes. Lesions in Leigh syndrome evolve over time and a lack of visible lesions does not exclude the diagnosis. Reversibility of lesions is seen in some patients, making the continued search for treatment and prevention a priority for clinicians and researchers.

Reversible Hydrolysis Reaction with the Spore Photoproduct under Alkaline Conditions.

PubMed

Adhikari, Surya; Lin, Gengjie; Li, Lei

2016-09-16

DNA lesions may reduce the electron density at the nucleobases, making them prone to further modifications upon the alkaline treatment. The dominant DNA photolesion found in UV-irradiated bacterial endospores is a thymine dimer, 5-thyminyl-5,6-dihydrothymine, i.e., the spore photoproduct (SP). Here we report a stepwise addition/elimination reaction in the SP hydrolysis product under strong basic conditions where a ureido group is added to the carboxyl moiety to form a cyclic amide, regenerating SP after eliminating a hydroxide ion. Direct amidation of carboxylic acids by reaction with amines in the presence of a catalyst is well documented; however, it is very rare for an amidation reaction to occur without activation. This uncatalyzed SP reverse reaction in aqueous solution is even more surprising because the carboxyl moiety is not a good electrophile due to the negative charge it carries. Examination of the base-catalyzed hydrolyses of two other saturated pyrimidine lesions, 5,6-dihydro-2'-deoxyuridine and pyrimidine (6-4) pyrimidone photoproduct, reveals that neither reaction is reversible even though all three hydrolysis reactions may share the same gem-diol intermediate. Therefore, the SP structure where the two thymine residues maintain a stacked conformation likely provides the needed framework enabling this highly unusual carboxyl addition/elimination reaction.

Determining mutation density using Restriction Enzyme Sequence Comparative Analysis (RESCAN)

USDA-ARS?s Scientific Manuscript database

The average mutation density of a mutant population is a major consideration when developing resources for the efficient, cost-effective implementation of reverse genetics methods such as Targeting of Induced Local Lesions in Genomes (TILLING). Reliable estimates of mutation density can be achieved ...

Magnetic resonance imaging in glenohumeral instability

PubMed Central

Jana, Manisha; Gamanagatti, Shivanand

2011-01-01

The glenohumeral joint is the most commonly dislocated joint of the body and anterior instability is the most common type of shoulder instability. Magnetic resonance (MR) imaging, and more recently, MR arthrography, have become the essential investigation modalities of glenohumeral instability, especially for pre-procedure evaluation before arthroscopic surgery. Injuries associated with glenohumeral instability are variable, and can involve the bones, the labor-ligamentous components, or the rotator cuff. Anterior instability is associated with injuries of the anterior labrum and the anterior band of the inferior glenohumeral ligament, in the form of Bankart lesion and its variants; whereas posterior instability is associated with reverse Bankart and reverse Hill-Sachs lesion. Multidirectional instability often has no labral pathology on imaging but shows specific osseous changes such as increased chondrolabral retroversion. This article reviews the relevant anatomy in brief, the MR imaging technique and the arthrographic technique, and describes the MR findings in each type of instability as well as common imaging pitfalls. PMID:22007285

Diagnosis of reversible causes of coma.

PubMed

Edlow, Jonathan A; Rabinstein, Alejandro; Traub, Stephen J; Wijdicks, Eelco F M

2014-12-06

Because coma has many causes, physicians must develop a structured, algorithmic approach to diagnose and treat reversible causes rapidly. The three main mechanisms of coma are structural brain lesions, diffuse neuronal dysfunction, and, rarely, psychiatric causes. The first priority is to stabilise the patient by treatment of life-threatening conditions, then to use the history, physical examination, and laboratory findings to identify structural causes and diagnose treatable disorders. Some patients have a clear diagnosis. In those who do not, the first decision is whether brain imaging is needed. Imaging should be done in post-traumatic coma or when structural brain lesions are probable or possible causes. Patients who do not undergo imaging should be reassessed regularly. If CT is non-diagnostic, a checklist should be used use to indicate whether advanced imaging is needed or evidence is present of a treatable poisoning or infection, seizures including non-convulsive status epilepticus, endocrinopathy, or thiamine deficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanisms of curcumin-induced gastroprotection against ethanol-induced gastric mucosal lesions.

PubMed

Czekaj, Renata; Majka, Jolanta; Magierowska, Katarzyna; Sliwowski, Zbigniew; Magierowski, Marcin; Pajdo, Robert; Ptak-Belowska, Agata; Surmiak, Marcin; Kwiecien, Slawomir; Brzozowski, Tomasz

2018-05-01

Curcumin, a pleiotropic substance used for centuries in traditional medicine, exhibits antioxidant, anti-inflammatory and antiproliferative efficacy against various tumours, but the role of curcumin in gastroprotection is little studied. We determined the effect of curcumin against gastric haemorrhagic lesions induced by 75% ethanol and alterations in gastric blood flow (GBF) in rats with cyclooxygenase-1 (COX-1) and COX-2 activity inhibited by indomethacin, SC-560 or rofecoxib, inhibited NO-synthase activity, capsaicin denervation and blockade of TRPV1 receptors by capsazepine. One hour after ethanol administration, the gastric mucosal lesions were assessed by planimetry, the GBF was examined by H 2 gas clearance, plasma gastrin was determined by radioimmunoassay, and the gastric mucosal mRNA expression of Cdx-2, HIF-1α, HO-1 and SOD 2 was analysed by RT-PCR. Curcumin, in a dose-dependent manner, reduced ethanol-induced gastric lesions and significantly increased GBF and plasma gastrin levels. Curcumin-induced protection was completely reversed by indomethacin and SC-560, and significantly attenuated by rofecoxib, L-NNA, capsaicin denervation and capsazepine. Curcumin downregulated Cdx-2 and Hif-1α mRNA expression and upregulated HO-1 and SOD 2, and these effects were reversed by L-NNA and further restored by co-treatment of L-NNA with L-arginine. Curcumin-induced protection against ethanol damage involves endogenous PG, NO, gastrin and CGRP released from sensory nerves due to activation of the vanilloid TRPV1 receptor. This protective effect can be attributed to the inhibition of HIF-1α and Cdx-2 expression and the activation of HO-1 and SOD 2 expression.

Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.

PubMed

Lu, Wen-Hsien; Hsieh, Kai-Sheng; Lu, Pei-Jung; Wu, Yi-Shan; Ho, Wen-Yu; Lai, Chi-Cheng; Wang, Jyh-Seng; Ger, Luo-Ping; Hsiao, Michael; Tseng, Ching-Jiunn

2013-05-01

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model. Treatment study. Research laboratory. Sprague-Dawley rats. We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker. The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours. Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

BIRDSHOT CHORIORETINITIS LESIONS ON INDOCYANINE GREEN ANGIOGRAPHY AS AN INDICATOR OF DISEASE ACTIVITY.

PubMed

Cao, Jennifer H; Silpa-Archa, Sukhum; Freitas-Neto, Clovis A; Foster, C Stephen

2016-09-01

To determine whether classical indocyanine green angiography lesions in patients with birdshot chorioretinitis can be used to monitor disease activity. A retrospective case series was performed on 26 eyes in 26 consecutive patients with birdshot chorioretinitis who had at least one indocyanine green angiography performed during disease activity and another during disease quiescence. Using Photoshop, the mean number, area, and area per spot on indocyanine green angiography were compared between disease activity and quiescence using a paired ratio test. The mean total lesion number, area, and area per spot during disease activity were 75.27 spots, 24,525 pixels, and 364 pixels/spots, respectively. The mean total lesion number, area, and area per spot size during disease quiescence were 28.35 spots (P < 0.01), 7,411 pixels (P < 0.01), and 279 pixels/spot (P = 0.12), respectively. There was a statistically significant decrease in the mean total area and number of lesions between the time of disease activity and disease quiescence (P < 0.01). Our results suggest that indocyanine green angiography has a role not only in diagnosis but also in monitoring treatment effectiveness; lesions can be reversible with treatment and their reappearance may be an indicator of disease relapse.

Spatial learning in rats: correlation with cortical choline acetyltransferase and improvement with NGF following NBM damage.

PubMed

Mandel, R J; Gage, F H; Thal, L J

1989-06-01

Rats display an acquisition deficit in a circular water maze following excitotoxic lesions of the nucleus basalis magnocellularis (NBM). Experiments were therefore performed to determine if acquisition behavior on this task could predict the degree of cortical cholinergic deafferentation and if the acquisition deficit could be pharmacologically reversed. Performance on acquisition was highly correlated with the lesion-induced reduction in cortical choline acetyltransferase (ChAT) activity. Accuracy of spatial behavior was highly correlated to percentage ChAT depletion (r = 0.75). Neither lesioned rats nor controls displayed a retention deficit after a 9-day interval, nor did either group display a passive-avoidance retention deficit. To test the causal relationship between cholinergic dysfunction and spatial behavior, the central nervous system cholinergic enhancer nerve growth factor (NGF) was intraventricularly infused for 4 weeks. NGF infusion resulted in improved acquisition of the water maze task compared to NBM-lesioned rats receiving vehicle infusion and untreated rats with NBM lesions. These studies indicate that the decrease in cortical ChAT activity is likely to be responsible for the observed acquisition deficit and that pharmacological manipulations can be successfully used to improve behavior following NBM lesions.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

PubMed

Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

2015-09-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Next-generation sequencing for targeted discovery of rare mutations in rice

USDA-ARS?s Scientific Manuscript database

Advances in DNA sequencing (i.e., next-generation sequencing, NGS) have greatly increased the power and efficiency of detecting rare mutations in large mutant populations. Targeting Induced Local Lesions in Genomes (TILLING) is a reverse genetics approach for identifying gene mutations resulting fro...

Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

PubMed Central

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

2014-01-01

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases.

PubMed

Alsadoun, Nadjla; MacGrogan, Gaëtan; Truntzer, Caroline; Lacroix-Triki, Magali; Bedgedjian, Isabelle; Koeb, Marie-Hélène; El Alam, Elsy; Medioni, Dan; Parent, Michel; Wuithier, Pascal; Robert, Isabelle; Boidot, Romain; Arnould, Laurent

2018-05-21

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors.

Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age.

PubMed

Counsell, Serena J; Shen, Yuji; Boardman, James P; Larkman, David J; Kapellou, Olga; Ward, Philip; Allsop, Joanna M; Cowan, Frances M; Hajnal, Joseph V; Edwards, A David; Rutherford, Mary A

2006-02-01

Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM.

Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism.

PubMed

Pfefferbaum, Adolf; Adalsteinsson, Elfar; Sullivan, Edith V

2006-07-01

Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.

Impact of Early and Late Visual Deprivation on the Structure of the Corpus Callosum: A Study Combining Thickness Profile with Surface Tensor-Based Morphometry.

PubMed

Shi, Jie; Collignon, Olivier; Xu, Liang; Wang, Gang; Kang, Yue; Leporé, Franco; Lao, Yi; Joshi, Anand A; Leporé, Natasha; Wang, Yalin

2015-07-01

Blindness represents a unique model to study how visual experience may shape the development of brain organization. Exploring how the structure of the corpus callosum (CC) reorganizes ensuing visual deprivation is of particular interest due to its important functional implication in vision (e.g., via the splenium of the CC). Moreover, comparing early versus late visually deprived individuals has the potential to unravel the existence of a sensitive period for reshaping the CC structure. Here, we develop a novel framework to capture a complete set of shape differences in the CC between congenitally blind (CB), late blind (LB) and sighted control (SC) groups. The CCs were manually segmented from T1-weighted brain MRI and modeled by 3D tetrahedral meshes. We statistically compared the combination of local area and thickness at each point between subject groups. Differences in area are found using surface tensor-based morphometry; thickness is estimated by tracing the streamlines in the volumetric harmonic field. Group differences were assessed on this combined measure using Hotelling's T(2) test. Interestingly, we observed that the total callosal volume did not differ between the groups. However, our fine-grained analysis reveals significant differences mostly localized around the splenium areas between both blind groups and the sighted group (general effects of blindness) and, importantly, specific dissimilarities between the LB and CB groups, illustrating the existence of a sensitive period for reorganization. The new multivariate statistics also gave better effect sizes for detecting morphometric differences, relative to other statistics. They may boost statistical power for CC morphometric analyses.

White matter disease and cognitive impairment in FMR1 premutation carriers.

PubMed

Filley, Christopher M; Brown, Mark S; Onderko, Karen; Ray, Megan; Bennett, Rachael E; Berry-Kravis, Elizabeth; Grigsby, Jim

2015-05-26

This cross-sectional, observational study examined the role of white matter involvement in the cognitive impairment of individuals with the fragile X mental retardation 1 (FMR1) premutation. Eight asymptomatic premutation carriers, 5 participants with fragile X tremor/ataxia syndrome (FXTAS), and 7 noncarrier controls were studied. The mean age of the asymptomatic premutation carriers, participants with FXTAS, and noncarrier controls was 60, 71, and 67 years, respectively. Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) were used to examine the middle cerebellar peduncles (MCP) and the genu and splenium of the corpus callosum in relation to executive function and processing speed. MRS measures were N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine, and fractional anisotropy (FA) was used for DTI. Executive function was assessed with the Behavioral Dyscontrol Scale and the Controlled Oral Word Association Test (COWAT), and processing speed with the Symbol Digit Modalities Test. Among all 13 FMR1 premutation carriers, significant correlations were found between N-acetyl aspartate/creatine and choline/creatine in the MCP and COWAT scores, and between FA in the genu and performance on the Behavioral Dyscontrol Scale, COWAT, and Symbol Digit Modalities Test; a correlation was also found between FA in the splenium and COWAT performance. In all regions studied, participants with FXTAS had the lowest mean FA. Microstructural white matter disease as determined by MRS and DTI correlated with executive dysfunction and slowed processing speed in these FMR1 premutation carriers. Neuroimaging abnormalities in the genu and MCP suggest that disruption of white matter within frontocerebellar networks has an important role in the cognitive impairment associated with the FMR1 premutation. © 2015 American Academy of Neurology.

Regionally-Specific Diffusion Tensor Imaging in Mild Cognitive Impairment and Alzheimer’s Disease

PubMed Central

Mielke, M.M.; Kozauer, N.A.; Chan, K.C.G.; George, M.; Toroney, J.; Zerrate, M.; Bandeen-Roche, K.; Wang, M-C; vanZijl, P.; Pekar, J.J.; Mori, S.; Lyketsos, C.G.; Albert, M.

2009-01-01

Background Diffusion tensor imaging (DTI) studies have shown significant cross-sectional differences among normal controls (Bozzali et al., 2002), mild cognitive impairment (Robbins et al.) and Alzheimer’s disease (AD) patients in several fiber tracts in the brain, but longitudinal assessment is needed. Methods We studied 75 participants (25 NC, 25 amnestic MCI, and 25 mild AD) at baseline and 3 months later, with both imaging and clinical evaluations. Fractional anisotropy (Bozzali et al., 2002) was analyzed in regions of interest (ROIs) in: (1) fornix, (2) cingulum bundle, (3) splenium, and (4) cerebral peduncles. Clinical data included assessments of clinical severity and cognitive function. Cross-sectional and longitudinal differences in FA, within each ROI, were analyzed with generalized estimating equations (GEE). Results Cross-sectionally, AD patients had lower FA than NC (p<0.05) at baseline and 3 months in the fornix and anterior portion of the cingulum bundle. Compared to MCI, AD cases had lower FA (p<0.05) in these regions and the splenium at 0 and 3 months. Both the fornix and anterior cingulum correlated across all clinical cognitive scores; lower FA in these ROIs corresponded to worse performance. Over the course of 3 months, when the subjects were clinically stable, the ROIs were also largely stable. Conclusions Using DTI, findings indicate FA is decreased in specific fiber tracts among groups of subjects that vary along the spectrum from normal to AD, and that this measure is stable over short periods of time. The fornix is a predominant outflow tract of the hippocampus and may be an important indicator of AD progression. PMID:19457371

IMPACT OF EARLY AND LATE VISUAL DEPRIVATION ON THE STRUCTURE OF THE CORPUS CALLOSUM: A STUDY COMBINING THICKNESS PROFILE WITH SURFACE TENSOR-BASED MORPHOMETRY

PubMed Central

Shi, Jie; Collignon, Olivier; Xu, Liang; Wang, Gang; Kang, Yue; Leporé, Franco; Lao, Yi; Joshi, Anand A.

2015-01-01

Blindness represents a unique model to study how visual experience may shape the development of brain organization. Exploring how the structure of the corpus callosum (CC) reorganizes ensuing visual deprivation is of particular interest due to its important functional implication in vision (e.g. via the splenium of the CC). Moreover, comparing early versus late visually deprived individuals has the potential to unravel the existence of a sensitive period for reshaping the CC structure. Here, we develop a novel framework to capture a complete set of shape differences in the CC between congenitally blind (CB), late blind (LB) and sighted control (SC) groups. The CCs were manually segmented from T1-weighted brain MRI and modeled by 3D tetrahedral meshes. We statistically compared the combination of local area and thickness at each point between subject groups. Differences in area are found using surface tensor-based morphometry; thickness is estimated by tracing the streamlines in the volumetric harmonic field. Group differences were assessed on this combined measure using Hotelling’s T2 test. Interestingly, we observed that the total callosal volume did not differ between the groups. However, our fine-grained analysis reveals significant differences mostly localized around the splenium areas between both blind groups and the sighted group (general effects of blindness) and, importantly, specific dissimilarities between the LB and CB groups, illustrating the existence of a sensitive period for reorganization. The new multivariate statistics also gave better effect sizes for detecting morphometric differences, relative to other statistics. They may boost statistical power for CC morphometric analyses. PMID:25649876

Deep white matter hyperintensities, microstructural integrity and dual task walking in older people.

PubMed

Ghanavati, Tabassom; Smitt, Myriam Sillevis; Lord, Stephen R; Sachdev, Perminder; Wen, Wei; Kochan, Nicole A; Brodaty, Henry; Delbaere, Kim

2018-01-03

To examine neural, physiological and cognitive influences on gait speed under single and dual-task conditions. Sixty-two community-dwelling older people (aged 80.0 ± 4.2 years) participated in our study. Gait speed was assessed with a timed 20-meter walk under single and dual-task (reciting alternate letters of the alphabet) conditions. Participants also underwent tests to estimate physiological fall risk based on five measures of sensorimotor function, cognitive function across five domains, brain white matter (WM) hyperintensities and WM microstructural integrity by measuring fractional anisotropy (FA). Univariate linear regression analyses showed that global physiological and cognitive measures were associated with single (β = 0.594 and β=-0.297, respectively) and dual-task gait speed (β = 0.306 and β=-0.362, respectively). Deep WMHs were associated with dual-task gait speed only (β = 0.257). Multivariate mediational analyses showed that global and executive cognition reduced the strength of the association between deep WMHs and dual-task gait speed by 27% (β = 0.188) and 44% (β = 0.145) respectively. There was a significant linear association between single-task gait speed and mean FA values of the genu (β=-0.295) and splenium (β=-0.326) of the corpus callosum, and between dual-task gait speed and mean FA values of Superior Cerebellar Peduncle (β=-0.284), splenium of the Corpus Callosum (β=-0.286) and Cingulum (β=-0.351). Greater deep WMH volumes are associated with slower walking speed under dual-task conditions, and this relationship is mediated in part by global cognition and executive abilities specifically. Furthermore, both cerebellum and cingulum are related to dual-task walking due to their role in motor skill performance and attention, respectively.

Callosal hyperintensities and gait speed gain from two types of mobility interventions in older adults.

PubMed

Nadkarni, Neelesh K; Perera, Subashan; Studenski, Stephanie A; Rosano, Caterina; Aizenstein, Howard J; VanSwearingen, Jessie M

2015-06-01

To assess whether the volume of callosal hyperintensities in the genu and splenium of older adults with mobility impairment is differentially associated with the degree of gain in gait speed after 2 types of gait interventions. Single-blind randomized controlled trial of 2 types of gait exercises in older adults. Research center in an academic institution. Ambulatory adults (N=44) aged ≥65 years with a slow and variable gait. Twelve-week physical therapist-guided trial of a conventional walking, endurance, balance, and strength (WEBS) intervention (n=20) versus a timing and coordination of gait (TC) intervention (n=22). Gain in gait speed after the intervention and its relation to callosal hyperintensities in the genu and splenium of the corpus callosum. Gait speed improved in both the WEBS group (mean change, 0.16m/s) and the TC group (mean change, 0.21m/s; both P<.05). The volume of white matter hypertintensities (WMHs) in the genu was differentially associated with gait speed gain (group × genual WMH interaction, P=.05). Greater genual WMH volume was related to a smaller gait speed gain in the WEBS group (P=.01) but not in the TC (P=.10) group. Splenial WMH volume was not differentially associated with gait speed gain (interaction, P=.90). Callosal hyperintensities differentially influence gait speed gain by the type of gait rehabilitation. Mobility impaired older adults with genual hyperintensities may benefit from a rehabilitation program focused on motor skill learning rather than on strength and endurance training. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Automated assessment of the remineralization of artificial enamel lesions with polarization-sensitive optical coherence tomography

PubMed Central

Lee, Robert C.; Kang, Hobin; Darling, Cynthia L.; Fried, Daniel

2014-01-01

Accurate measurement of the highly mineralized transparent surface layer that forms on caries lesions is important for diagnosis of the lesion activity because chemical intervention can slow or reverse the caries process via remineralization. Previous in-vitro and in-vivo studies have demonstrated that polarization-sensitive optical coherence tomography (PS-OCT) can nondestructively image the subsurface lesion structure and the highly mineralized transparent surface zone of caries lesions. The purpose of this study was to develop an approach to automatically process 3-dimensional PS-OCT images and to accurately assess the remineralization process in simulated enamel lesions. Artificial enamel lesions were prepared on twenty bovine enamel blocks using two models to produce varying degree of demineralization and remineralization. The thickness of the transparent surface layer and the integrated reflectivity of the subsurface lesion were measured using PS-OCT. The automated transparent surface layer detection algorithm was able to successfully detect the transparent surface layers with high sensitivity ( = 0.92) and high specificity ( = 0.97). The estimated thickness of the transparent surface layer showed a strong correlation with polarized light microscopy (PLM) measurements of all regions (R2 = 0.90). The integrated reflectivity, ΔR, and the integrated mineral loss, ΔZ, showed a moderate correlation (R2 = 0.32). This study demonstrates that PS-OCT can automatically measure the changes in artificial enamel lesion structure and severity upon exposure to remineralization solutions. PMID:25401009

Fractionating the Binding Process: Neuropsychological Evidence from Reversed Search Efficiencies

ERIC Educational Resources Information Center

Humphreys, Glyn W.; Hodsoll, John; Riddoch, M. Jane

2009-01-01

The authors present neuropsychological evidence distinguishing binding between form, color, and size (cross-domain binding) and binding between form elements. They contrasted conjunctive search with difficult feature search using control participants and patients with unilateral parietal or fronto/temporal lesions. To rule out effects of task…

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mouret, Stéphane, E-mail: stephane.mouret@irba.fr; Wartelle, Julien; Emorine, Sandy

2013-10-15

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated inmore » this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.« less

Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

PubMed

Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

2001-11-30

Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [35S]GTPgammaS binding) at cloned hD2 (and hD3) receptors. At rat striatal membranes, dopamine stimulated [35S]GTPgammaS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D2/D3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D2 receptor antagonist, L741,626. Further, novel antagonists selective for D3 and D4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D3 and D4 receptor-selective doses of S33084 and S18126, respectively. In functional ([35S]GTPgammaS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (approximately 50% stimulation), but significantly greater on the lesioned side (approximately 80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion, the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D2, but not D3 or D4, receptor-mediated G-protein activation.

PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB.

PubMed

Faria, Daniele de Paula; Copray, Sjef; Sijbesma, Jurgen W A; Willemsen, Antoon T M; Buchpiguel, Carlos A; Dierckx, Rudi A J O; de Vries, Erik F J

2014-05-01

In this study, we compared the ability of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). The kinetics of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [(11)C]CIC make this tracer less suitable for in vivo PET imaging. [(11)C]PIB showed good uptake in the white matter in the cerebrum, but [(11)C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [(11)C]MeDAS distribution correlated well with myelin density in different brain regions. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [(11)C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [(11)C]CIC and [(11)C]PIB.

Comparison of Reversibility of Rat Forestomach Lesions Induced by Genotoxic and Non‐genotoxic Carcinogens

PubMed Central

Kagawa, Masataka; Hakoi, Kazuo; Yamamoto, Atsushi; Futakuchi, Mitsuru

1993-01-01

Reversibility of forestomach lesions induced by genotoxic and non‐genotoxic carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats were given dietary 0.1% 8‐nitroquinoline, dietary 0.4–0.2% 2‐(2‐furyl)‐3‐(5‐nitro‐2‐furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N‐methyl‐N′‐nitro‐N‐nitrosoguanidine once a week, or 20 ppm N‐methylnitrosourethane in the drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2% caffeic acid, 2% sesamol or 2% 4‐methoxyphenol in the diet as a non‐genotoxic carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24. Half of the remainder were maintained on basal diet alone for an additional 24 weeks and the other half were given the same chemical for 48 weeks, and then killed. Forestomach lesions induced by genotoxic carcinogens did not regress after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH), but not basal cell hyperplasia (BCH), induced by non‐genotoxic carcinogens clearly regressed after cessation of insult. SFH labeling indices in the non‐genotoxic carcinogen‐treated cases decreased after removal of the carcinogenic stimulus whereas BCH values were low irrespective of treatment. Atypical hyperplasia (AH), observed at high incidences in rats treated with genotoxic carcinogens, was also evident in animals receiving non‐genotoxic agents, even after their withdrawal, albeit at low incidences. AH labeling indices remained high even without continued insult. These results indicate that even with non‐genotoxic carcinogens, heritable alterations at the DNA level could occur during strong cell proliferation and result in AH development. This putative preneoplastic lesion might then progress to produce carcinomas. PMID:8276717

The imaging spectrum of posterior reversible encephalopathy syndrome: A pictorial review.

PubMed

Brady, Emily; Parikh, Neal S; Navi, Babak B; Gupta, Ajay; Schweitzer, Andrew D

Posterior reversible encephalopathy syndrome (PRES) is characterized by the acute onset of neurologic symptoms (headache, altered mental status, visual changes, seizures) with accompanying vasogenic edema on brain imaging. Risk factors for PRES include infection, uremia, malignancy, autoimmune disorders, the peripartum state and hypertension. PRES is classically described as being posterior (i.e. parieto-occipital) but radiologic variants are increasingly recognized. This pictorial review demonstrates the heterogeneity of the different radiologic presentations of PRES in reference to lesion distribution, hemorrhage, diffusion restriction, contrast enhancement, and other associated findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Benign colonic metaplasia at a previous stoma site in a patient without adenomatous polyposis.

PubMed

Prouty, Megan; Patrawala, Samit; Vogt, Adam; Kelleher, Michael; Lee, Michael; Parker, Douglas C

2016-03-01

There are few reported cases of cutaneous intestinal metaplasia or primary adenocarcinoma arising at the ileostomy site following panproctocolectomy. These complications have been seen almost exclusively in patients with familial adenomatous polyposis and inflammatory bowel disease (IBD). However, benign intraepidermal colonic mucosa at a reversed ileostomy site in a patient without familial adenomatous polyposis or IBD has not been documented. We report a case of a 51-year-old female with a history of colonic adenocarcinoma who presented with pruritic, erythematous, scaly plaques on the right lower abdomen, present since reversal of her ileostomy in 2007. Skin biopsy revealed benign foci of colonic epithelium with no evidence of adenomatous change. Benign intraepidermal colonic mucosa was diagnosed based on histopathologic findings and immunohistochemistry. To our knowledge, this is the first case of intraepidermal benign colonic metaplasia forming in a patient following ostomy reversal. The case emphasizes the importance of patient education and physical examination of the stoma or stoma remnants for detection of unusual or changing lesions due to the risk for malignant transformation. It also demonstrates that benign colonic mucosa should be considered in the differential diagnosis when evaluating lesions near ileostomy sites, regardless of whether the patient has a history of familial adenomatous polyposis or IBD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Medial Prefrontal Administration of MK-801 Impairs T-maze Discrimination Reversal Learning in Weanling Rats

PubMed Central

Watson, Deborah J.; Stanton, Mark E.

2009-01-01

Several executive functions rely on the medial prefrontal cortex (mPFC) in the rat. Aspiration and neurotoxic lesions of the mPFC impair reversal learning in adult rats [1, 16, 34, 55]. Systemic administration of MK-801, an NMDA receptor antagonist, impairs T-maze reversal learning in weanling rats but the role of mPFC NMDA receptor antagonism in this effect is not known in either adult or young animals. This set of studies showed that mPFC NMDA receptors are specifically involved in T-maze discrimination reversal in weanling rats. In Experiment 1, 26-day-old rats (P26) demonstrated a dose-dependent impairment following bilateral mPFC administration of either 2.5 or 5.0 µg MK-801 or saline (vehicle) during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but 4 groups of rats received bilateral mPFC infusions during acquisition only (MK-SAL), reversal only (SAL-MK), both phases (MK-MK) or neither phase (SAL-SAL). MK-801 impaired performance only when infused during reversal. This suggests that NMDA receptor antagonism in the mPFC is selectively involved in reversal learning during development and this may account for the previously reported effects of systemic MK-801 on T-maze discrimination reversal in weanling rats. PMID:19643149

Efficacy of Concomitant Therapy with Fluoride and Chlorhexidine Varnish on Remineralization of Incipient Lesions in Young Children

PubMed Central

Tandon, Shobha; Nayak, Rashmi; Ratnanag, P Venkat; Prajapati, Deepesh; Kamath, Namitha

2016-01-01

Aim To assess the effect of combined use of chlorhexidine and fluoride varnish on the remineralization of incipient carious lesions in young children. Materials and methods Twenty caries-active children (80 lesions) were randomly divided into four groups and subjected to initial examination. Caries status was assessed visually and with the aid of DIAGNOdent. Baseline enamel biopsies were obtained. Subjects of groups I and II received fluoride and chlorhexidine varnish respectively. Group III received both fluoride and chlorhexidine varnish alternatively, for a period of 4 weeks. Group IV served as the control. At 3-month follow-up, the incipient lesions were assessed again with DIAGNOdent and enamel biopsy. Results Increased calcium, phosphate, and fluoride levels were noticed in groups I, II, III compared to group IV, at the 3-month follow-up (p < 0.001). Conclusion The combined therapy with fluoride and chlorhex-idine varnish may be considered an alternative therapy for early reversal of incipient lesions. How to cite this article Naidu S, Tandon S, Nayak R, Ratnanag PV, Prajapati D, Kamath N. Efficacy of Concomitant Therapy with Fluoride and Chlorhexidine Varnish on Remineralization of Incipient Lesions in Young Children. Int J Clin Pediatr Dent 2016;9(4):296-302. PMID:28127159

Imaging and detection of early stage dental caries with an all-optical photoacoustic microscope

NASA Astrophysics Data System (ADS)

Hughes, D. A.; Sampathkumar, A.; Longbottom, C.; Kirk, K. J.

2015-01-01

Tooth decay, at its earliest stages, manifests itself as small, white, subsurface lesions in the enamel. Current methods for detection in the dental clinic are visual and tactile investigations, and bite-wing X-ray radiographs. These techniques suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease due to the small size (<100μm) of the lesion. A fine-resolution (600 nm) ultra-broadband (200 MHz) all-optical photoacoustic microscopy system was is used to image the early signs of tooth decay. Ex-vivo tooth samples exhibiting white spot lesions were scanned and were found to generate a larger (one order of magnitude) photoacoustic (PA) signal in the lesion regions compared to healthy enamel. The high contrast in the PA images potentially allows lesions to be imaged and measured at a much earlier stage than current clinical techniques allow. PA images were cross referenced with histology photographs to validate our experimental results. Our PA system provides a noncontact method for early detection of white-spot lesions with a high detection bandwidth that offers advantages over previously demonstrated ultrasound methods. The technique provides the sensing depth of an ultrasound system, but with the spatial resolution of an optical system.

Successful Treatment of Lung Calciphylaxis With Sodium Thiosulfate in a Patient With Sickle Cell Disease

PubMed Central

Arrestier, Romain; Dudreuilh, Caroline; Remy, Philippe; Boulahia, Ghada; Bentaarit, Bouteina; Leibler, Claire; Adedjouma, Amir; Kofman, Tomek; Matignon, Marie; Sahali, Dil; Dufresne, Roger; Deux, Jean-Francois; Colin, Charlotte; Grimbert, Philippe; Lang, Philippe; Bartolucci, Pablo; Maitre, Bernard; Tran Van Nhieu, Jeanne; Audard, Vincent

2016-01-01

Abstract Calciphylaxis is a small vessel vasculopathy, characterized by medial wall calcification that develops in a few patients with chronic renal failure. The prognosis of skin calciphylaxis has improved considerably since the introduction of sodium thiosulfate (STS), but it remains unclear whether this therapy is effective against organ lesions related to calciphylaxis. Pulmonary calciphylaxis is a usually fatal medical condition that may occur in association with skin involvement in patients with end-stage renal disease. We report here the case of a 49-year-old woman homozygous sickle cell disease patient on chronic hemodialysis with biopsy-proven systemic calciphylaxis involving the lungs and skin. On admission, ulcerative skin lesions on the lower limbs and bilateral pulmonary infiltrates on chest computerized tomography scan were the main clinical and radiological findings. Skin and bronchial biopsies demonstrated calciphylaxis lesions. The intravenous administration of STS in association with cinacalcet for 8 consecutive months led to a clear improvement in skin lesions and thoracic lesions on chest computerized tomography scan. This case suggests for the first time that organ lesions related to calciphylaxis, and particularly lung injury, are potentially reversible. This improvement probably resulted from the combination of 3 interventions (more frequent dialysis, cinacalcet, and STS), rather than the administration of STS alone. PMID:26871829

Insights into the Virulence Traits of Streptococcus mutans in Dentine Carious Lesions of Children with Early Childhood Caries.

PubMed

Bezerra, Daniela S; Stipp, Rafael N; Neves, Beatriz G; Guedes, Sarah F F; Nascimento, Marcelle M; Rodrigues, Lidiany K A

2016-01-01

Streptococcus mutans is an oral bacterium considered to play a major role in the development of dental caries. This study aimed to investigate the prevalence of S. mutans in active and arrested dentine carious lesions of children with early childhood caries and to examine the expression profile of selected S. mutans genes associated with survival and virulence, within the same carious lesions. Dentine samples were collected from 29 active and 16 arrested carious lesions that were diagnosed in preschool children aged 2-5 years. Total RNA was extracted from the dentine samples, and reverse transcription quantitative real-time PCR analyses were performed for the quantification of S. mutans and for analyses of the expression of S. mutans genes associated with bacterial survival (atpD, nox, pdhA) and virulence (fabM and aguD). There was no statistically significant difference in the prevalence of S. mutans between active and arrested carious lesions. Expression of the tested genes was detected in both types of carious dentine. The pdhA (p = 0.04) and aguD (p = 0.05) genes were expressed at higher levels in arrested as compared to active lesions. Our findings revealed that S. mutans is part of the viable microbial community in active and arrested dentine carious lesions. The increase in expression of the pdhA and aguD genes in arrested lesions is likely due to the unfavourable environmental conditions for microbial growth, inherent to this type of lesions. © 2016 S. Karger AG, Basel.

Persistent Left Unilateral Mirror Writing: A Neuropsychological Case Study

ERIC Educational Resources Information Center

Angelillo, Valentina G.; De Lucia, Natascia; Trojano, Luigi; Grossi, Dario

2010-01-01

Mirror writing (MW) is a rare disorder in which a script runs in direction opposite to normal and individual letters are reversed. The disorder generally occurs after left-hemisphere lesions, is transient and is observed on the left hand, whereas usually motor impairments prevent assessment of direction of right handwriting. We describe a…

West Nile Virus Encephalitis in a Barbary Macaque (Macaca sylvanus)

PubMed Central

Barker, Ian K.; Crawshaw, Graham J.; Bertelsen, Mads F.; Drebot, Michael A.; Andonova, Maya

2004-01-01

An aged Barbary ape (Macaca sylvanus) at the Toronto Zoo became infected with naturally acquired West Nile virus (WNV) encephalitis that caused neurologic signs, which, associated with other medical problems, led to euthanasia. The diagnosis was based on immunohistochemical assay of brain lesions, reverse transcriptase–polymerase chain reaction, and virus isolation. PMID:15200866

Use of a polysulfone hemodialysis membrane may prevent recurrent posterior reversible encephalopathy syndrome in a patient undergoing hemodialysis.

PubMed

Mima, Akira; Matsubara, Takeshi; Endo, Shuichiro; Murakami, Taichi; Hashimoto, Yasuki

2014-01-01

A 71-year-old woman underwent hemodialysis (HD) treatment for chronic kidney disease. During HD, she developed headache, abnormalities in visual perception, and generalized convulsion. Brain magnetic resonance imaging (MRI) showed T2-hyperintensity lesions in the posterior lobe, and an electroencephalogram showed slow waves in all areas. Twenty days later, the T2-hyperintensity lesions had vanished. Furthermore, perfusion computed tomography (CT) and single-photon emission CT with N-isopropyl[(123)I]-p-iodoamphetamine (IMP-SPECT) showed no significant abnormalities. The patient was diagnosed with posterior reversible encephalopathy syndrome (PRES) because she displayed typical clinical symptoms and MRI findings. Although several antihypertensive and antiseizure medications were administered, the patient experienced recurrent PRES. Therefore, we used a polysulfone dialyzer to reduce the oxidative stress and inflammation while preserving vascular endothelial function. After use of a polysulfone dialyzer membrane, the patient had no PRES episodes during the clinical course. This is the first study to demonstrate that use of a polysulfone dialyzer membrane instead of a cellulose membrane may prevent recurrent PRES.

Periodic alternating nystagmus during caloric stimulation.

PubMed

Taki, Masakatsu; Hasegawa, Tatsuhisa; Adachi, Naoko; Fujita, Tomoki; Sakaguchi, Hirofumi; Hisa, Yasuo

2014-04-01

Periodic alternating nystagmus (PAN) is a form of horizontal jerk nystagmus characterized by periodic reversals in direction. We report a case who exhibited transient PAN induced by caloric stimulation. The patient was a 75-year-old male. He had experienced floating sensation in January 2010. Eight months later, he was referred to our university hospital. Gaze nystagmus and positional tests revealed no nystagmus. Only weak right-beating horizontal nystagmus was observed during left Dix-Hallpike maneuver. Electronystagmography showed normal saccadic and smooth pursuit eye movements. The optokinetic nystagmus pattern test was also bilaterally normal. However, during the caloric stimulation to the right ear, at 166 s from the start of irrigation, the direction of nystagmus alternated from leftward to rightward, and thereafter this reversal of direction repeated 15 times. Magnetic resonance imaging showed no significant lesion except for chronic ischemia in the brain. The patient probably had some kind of latent lesion of impaired velocity storage and exhibited transient PAN induced by caloric stimulation. Caloric stimulation is useful and simple examination to disclose latent eye movement disorders of which velocity storage mechanism is impaired. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys.

PubMed

Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F; Mir, Anis; Schwab, Martin E; Belhaj-Saif, Abderraouf; Rouiller, Eric M

2013-01-01

In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns ("true" recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

Immunotoxic cholinergic lesions in the basal forebrain reverse the effects of entorhinal cortex lesions on conditioned odor aversion in the rat.

PubMed

Ferry, Barbara; Herbeaux, Karin; Cosquer, Brigitte; Traissard, Natalia; Galani, Rodrigue; Cassel, Jean-Christophe

2007-07-01

Conditioned odor aversion (COA) corresponds to the avoidance of an odorized-tasteless solution (conditioned stimulus, CS) previously paired with toxicosis. COA occurs only when the interstimulus interval (ISI) is kept short, suggesting that the memory trace of the odor is subject to rapid decay. Previous experiments have shown that the entorhinal cortex (EC) is involved in the acquisition of COA, since lesion of the EC rendered COA tolerant to long ISI. Because EC lesions induce a septo-hippocampal cholinergic sprouting, the present experiment investigated whether COA tolerance to long ISI may be linked to this sprouting reaction. In a first experiment, male Long-Evans rats subjected to bilateral excitotoxic EC lesions combined to intracerebroventricular infusions of the selective cholinergic immunotoxin 192 IgG-saporin were exposed to odor-toxicosis pairing using a long ISI (120 min). Results showed that EC-lesioned rats displayed COA with the long ISI but not the control groups. In rats with EC combined to 192 IgG-saporin lesions, histological analysis demonstrated no evidence for cholinergic septo-hippocampal sprouting. In a second experiment, animals with 192-IgG saporin lesion showed a marked COA with a short ISI (5 min). These results suggest that the COA with the long ISI found in rats with EC lesions might involve a functional activity related to the EC lesion-induced hippocampal cholinergic sprouting. As the injection of 192 IgG-saporin alone did not affect COA with a short ISI, our data also point to a possible role of hippocampal cholinergic neurons in the modulation of memory processes underlying COA.

Comparison of Functional Recovery of Manual Dexterity after Unilateral Spinal Cord Lesion or Motor Cortex Lesion in Adult Macaque Monkeys

PubMed Central

Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F.; Mir, Anis; Schwab, Martin E.; Belhaj-Saif, Abderraouf; Rouiller, Eric M.

2013-01-01

In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns (“true” recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex. PMID:23885254

Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats.

PubMed

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I; Holschneider, Daniel P

2015-01-01

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson's disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (1) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (2) emergence of the ventrolateral striatum as a new broadly connected network hub; and (3) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the parkinsonian rats, which could underlie recovery in motor functions observed in these animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative graphical analysis of simultaneous dynamic PET/MRI for assessment of prostate cancer.

PubMed

Rosenkrantz, Andrew B; Koesters, Thomas; Vahle, Anne-Kristin; Friedman, Kent; Bartlett, Rachel M; Taneja, Samir S; Ding, Yu-Shin; Logan, Jean

2015-04-01

Dynamic FDG imaging for prostate cancer characterization is limited by generally small size and low uptake in prostate tumors. Our aim in this pilot study was to explore feasibility of simultaneous PET/MRI to guide localization of prostate lesions for dynamic FDG analysis using a graphical approach. Three patients with biopsy-proven prostate cancer underwent simultaneous FDG PET/MRI, incorporating dynamic prostate imaging. Histology and multiparametric MRI findings were used to localize tumors, which in turn guided identification of tumors on FDG images. Regions of interest were manually placed on tumor and benign prostate tissue. Blood activity was extracted from a region of interest placed on the femoral artery on PET images. FDG data were analyzed by graphical analysis using the influx constant Ki (Patlak analysis) when FDG binding seemed irreversible and distribution volume VT (reversible graphical analysis) when FDG binding seemed reversible given the presence of washout. Given inherent coregistration, simultaneous acquisition facilitated use of MRI data to localize small lesions on PET and subsequent graphical analysis in all cases. In 2 cases with irreversible binding, tumor had higher Ki than benign using Patlak analysis (0.023 vs 0.006 and 0.019 vs 0.008 mL/cm3 per minute). In 1 case appearing reversible, tumor had higher VT than benign using reversible graphical analysis (0.68 vs 0.52 mL/cm3). Simultaneous PET/MRI allows localization of small prostate tumors for dynamic PET analysis. By taking advantage of inclusion of the femoral arteries in the FOV, we applied advanced PET data analysis methods beyond conventional static measures and without blood sampling.

The hallucinogen DOI reduces low-frequency oscillations in rat prefrontal cortex: reversal by antipsychotic drugs.

PubMed

Celada, Pau; Puig, M Victoria; Díaz-Mataix, Llorenç; Artigas, Francesc

2008-09-01

Perceptual and psychic alterations and thought disorder are fundamental elements of schizophrenia symptoms, a pathology associated with an abnormal macro- and microcircuitry of several brain areas including the prefrontal cortex (PFC). Alterations in information processing in PFC may partly underlie schizophrenia symptoms. The 5-HT(2A/2C) agonist DOI and antipsychotic drugs were administered to anesthetized rats. Single unit and local field potential (LFP) extracellular recordings were made in medial PFC (mPFC). Electrolytic lesions were performed in the thalamic nuclei. DOI markedly disrupts cellular and network activity in rat PFC. DOI altered pyramidal discharge in mPFC (39% excited, 27% inhibited, 34% unaffected; n = 51). In all instances, DOI concurrently reduced low-frequency oscillations (.3-4 Hz; power spectrum: .25 +/- .02 and .14 +/- .01 microV(2) in basal conditions and after 50-300 microg/kg intravenous (i.v.) DOI, respectively; n = 51). Moreover, DOI disrupted the temporal association between the active phase of LFP and pyramidal discharge. Both effects were reversed by M100907 (5-HT(2A) receptor antagonist) and were not attenuated by thalamic lesions, supporting an intracortical origin of the effects of DOI. The reduction in low-frequency oscillations induced by DOI was significantly reversed by the antipsychotic drugs haloperidol (.1-.2 mg/kg i.v.) and clozapine (1 mg/kg i.v.). DOI disorganizes network activity in PFC, reducing low-frequency oscillations and desynchronizing pyramidal discharge from active phases of LFP. These effects may underlie DOI's psychotomimetic action. The reversal by clozapine and haloperidol indicates that antipsychotic drugs may reduce psychotic symptoms by normalizing an altered PFC function.

Structural Imaging Measures of Brain Aging

PubMed Central

Lockhart, Samuel N.

2014-01-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society. PMID:25146995

Structural imaging measures of brain aging.

PubMed

Lockhart, Samuel N; DeCarli, Charles

2014-09-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

Dental caries: a dynamic disease process.

PubMed

Featherstone, J D B

2008-09-01

Abstract Dental caries is a transmissible bacterial disease process caused by acids from bacterial metabolism diffusing into enamel and dentine and dissolving the mineral. The bacteria responsible produce organic acids as a by-product of their metabolism of fermentable carbohydrates. The caries process is a continuum resulting from many cycles of demineralization and remineralization. Demineralization begins at the atomic level at the crystal surface inside the enamel or dentine and can continue unless halted with the end-point being cavitation. There are many possibilities to intervene in this continuing process to arrest or reverse the progress of the lesion. Remineralization is the natural repair process for non-cavitated lesions, and relies on calcium and phosphate ions assisted by fluoride to rebuild a new surface on existing crystal remnants in subsurface lesions remaining after demineralization. These remineralized crystals are acid resistant, being much less soluble than the original mineral.

Transient anterior subcapsular vacuolar change of the crystalline lens in patients after posterior chamber phakic intraocular lens implantation.

PubMed

Chung, Jin Kwon; Shin, Jin Hee; Lee, Sung Jin

2013-10-25

We present two cases of transient vacuolar changes in the anterior subcapsular space of the crystalline lens in patients after posterior chamber phakic intraocular lens implantation. Implantable collamer lenses (ICL) were implanted in healthy myopic patients. Vacuolar changes developed just after the irrigating procedure through the narrow space between the ICL and the crystalline lens. Slit-lamp examinations and spectral domain optical coherence tomography showed bleb-like lesions in the anterior subcapsular space of one eye in each case, though the lesions gradually improved without visual deterioration. Consequently, the lesions turned into a few anterior subcapsular small faint opacities. Direct irrigation of the narrow space confined by the ICL and the crystalline lens is at risk for the development of vacuolar changes in the crystalline lens. The observed spontaneous reversal indicates that surgeons should not rush to surgical intervention but rather opt for close follow over several weeks.

Reliability of store and forward teledermatology for skin neoplasms.

PubMed

Warshaw, Erin M; Gravely, Amy A; Nelson, David B

2015-03-01

Teledermatology may be less optimal for skin neoplasms than for rashes. We sought to determine agreement for skin neoplasms. This was a repeated measures study. Each lesion was examined by a clinic dermatologist and a teledermatologist; both generated a primary diagnosis, up to 2 differential diagnoses, and management. Macro images and polarized light dermoscopy images were obtained; for pigmented lesions only, contact immersion dermoscopy image was obtained. There were 3021 lesions in 2152 patients. Of 1685 biopsied lesions, there were 410 basal cell carcinomas (24%), 240 squamous cell carcinomas (14%), and 41 melanomas (2.4%). Agreement was fair to substantial for primary diagnosis (45.7%-80.1%; kappa 0.32-0.62), substantial to almost perfect for aggregated diagnoses (primary plus differential; 78.6%-93.9%; kappa 0.77-0.90), and fair for management (66.7%-86.1%; kappa 0.28-0.41). Diagnostic agreement rates were higher for pigmented lesions (52.8%-93.9%; kappa 0.44-0.90) than nonpigmented lesions (47.7%-87.3%; kappa 0.32-0.86), whereas the reverse was found for management agreement (pigmented: 66.7%-79.8%, kappa 0.19-0.35 vs nonpigmented: 72.0%-86.1%, kappa 0.38-0.41). Agreement rates using macro images were similar to polarized light dermoscopy; contact immersion dermoscopy, however, significantly improved rates for pigmented lesions. We studied a homogeneous population. Diagnostic agreement was moderate to almost perfect whereas management agreement was fair. Polarized light dermoscopy increased rates modestly whereas contact immersion dermoscopy significantly increased rates for pigmented lesions. Published by Elsevier Inc.

A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

PubMed

Baek, Hyun Seok; Lee, Se-Jin

2015-01-01

Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and recovery of laser-induced retinal injury in rats

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Epstein, Yoram; Rosner, Mordechai

2005-04-01

Retinal photocoagulation lesions undergo primary and secondary degeneration followed by partial healing. This study follows the sequential changes in laser-induced retinal lesion over a time span of 60 days. Argon laser lesions were created in 36 pigmented rats. Sections of the retinal lesions were evaluated by light microscopy 1, 24, 48, 72 hours, and 20, and 60 days after the injury (six animals at each time point). The diameter of the lesion was equal to that of the laser spot 1h after irradiation and increased by 24h. It decreased later, slightly during the following 48h and significantly by 20 days. The destruction of photoreceptors was most severe after 24-48h. The nuclei in the outer-nuclear layer were pyknotic at the lesion site at 1h and disappeared later. Healing processes began 72h after the irradiation and was completed by 60 days. Filling-in by sliding of near nuclei was observed by the 60th day. Reversible changes were seen also in the retinal pigment epithelium (with formation of a plaque at 72h and its degradation later on) and in the choroid (disorganization of capillaries by 48h with later reorganization). Conclusions: The development of a laser-induced injury is gradual. The photoreceptors are damaged first and than the damage spreads to other layers of retina and to areas adjacent the primary injury site. The extension of the damage is later stopped and the adjacent tissues tend to fill the lesion and remodel the retina.

[Hyperbaric oxygen therapy and inert gases in cerebral ischemia and traumatic brain injury].

PubMed

Chhor, V; Canini, F; De Rudnicki, S; Dahmani, S; Gressens, P; Constantin, P

2013-12-01

Cerebral ischemia is a common thread of acute cerebral lesions, whether vascular or traumatic origin. Hyperbaric oxygen (HBO) improves tissue oxygenation and may prevent impairment of reversible lesions. In experimental models of cerebral ischemia or traumatic brain injury, HBO has neuroprotective effects which are related to various mechanisms such as modulation of oxidative stress, neuro-inflammation or cerebral and mitochondrial metabolism. However, results of clinical trials failed to prove any neuroprotective effects for cerebral ischemia and remained to be confirmed for traumatic brain injury despite preliminary encouraging results. The addition of inert gases to HBO sessions, especially argon or xenon which show neuroprotective experimental effects, may provide an additional improvement of cerebral lesions. Further multicentric studies with a strict methodology and a better targeted definition are required before drawing definitive conclusions about the efficiency of combined therapy with HBO and inert gases in acute cerebral lesions. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Identification of disappearing brain lesions with intraoperative magnetic resonance imaging prevents surgery.

PubMed

Sutherland, Christina S; Kelly, John Jp; Morrish, William; Sutherland, Garnette R

2010-10-01

Typically, neurosurgery is performed several weeks after diagnostic imaging. In the majority of cases, histopathology confirms the diagnosis of neoplasia. In a small number of cases, a different diagnosis is established or histopathology is nondiagnostic. The frequency with which these outcomes occur has not been established. To determine the frequency and outcome of disappearing brain lesions within a group of patients undergoing surgery for suspected brain tumor. Over the past decade, 982 patients were managed in the intraoperative magnetic resonance imaging unit at the University of Calgary, Calgary, Alberta, Canada. These patients have been prospectively evaluated. In 652 patients, a brain tumor was suspected. In 6 of the 652 patients, histopathology indicated a nontumor diagnosis. In 5 patients, intraoperative images, acquired after induction of anesthesia, showed complete or nearly complete resolution of the suspected tumor identified on diagnostic magnetic resonance imaging acquired 6 ± 4 (mean ± SD) weeks previously. Anesthesia was reversed, and the surgical procedure aborted. The lesions have not progressed with 6 ± 2 years of follow-up. Intraoperative magnetic resonance imaging prevented surgery on 5 patients with disappearing lesions.

Salient lesions in domestic ruminants infected with the emerging so-called Schmallenberg virus in Germany.

PubMed

Herder, V; Wohlsein, P; Peters, M; Hansmann, F; Baumgärtner, W

2012-07-01

The so-called Schmallenberg virus (SBV), first detected in a German town of the same name in October 2011, is a novel emerging orthobunyavirus in Europe causing malformations and severe economic loss in ruminants. This report describes lesions in 40 sheep, 2 goats, and 16 cattle naturally infected with SBV as determined by real-time quantitative reverse transcription polymerase chain reaction. The most common macroscopic changes were arthrogryposis, vertebral malformations, brachygnathia inferior, and malformations of the central nervous system, including hydranencephaly, porencephaly, hydrocephalus, cerebellar hypoplasia, and micromyelia. Histologic lesions included lymphohistiocytic meningoencephalomyelitis in some cases, glial nodules mainly in the mesencephalon and hippocampus of lambs and goats, and neuronal degeneration and necrosis mainly in the brain stem of calves. Micromyelia was characterized by a loss of gray and white matter, with few neurons remaining in the ventral horn in calves. The skeletal muscles had myofibrillar hypoplasia in lambs and calves. The lesions of SBV-associated abortion and perinatal death are similar to those attributed to Akabane virus and other viruses in the Simbu group of bunyaviruses.

The neural substrates of deliberative decision making: contrasting effects of hippocampus lesions on performance and vicarious trial-and-error behavior in a spatial memory task and a visual discrimination task

PubMed Central

Bett, David; Allison, Elizabeth; Murdoch, Lauren H.; Kaefer, Karola; Wood, Emma R.; Dudchenko, Paul A.

2012-01-01

Vicarious trial-and-errors (VTEs) are back-and-forth movements of the head exhibited by rodents and other animals when faced with a decision. These behaviors have recently been associated with prospective sweeps of hippocampal place cell firing, and thus may reflect a rodent model of deliberative decision-making. The aim of the current study was to test whether the hippocampus is essential for VTEs in a spatial memory task and in a simple visual discrimination (VD) task. We found that lesions of the hippocampus with ibotenic acid produced a significant impairment in the accuracy of choices in a serial spatial reversal (SR) task. In terms of VTEs, whereas sham-lesioned animals engaged in more VTE behavior prior to identifying the location of the reward as opposed to repeated trials after it had been located, the lesioned animals failed to show this difference. In contrast, damage to the hippocampus had no effect on acquisition of a VD or on the VTEs seen in this task. For both lesion and sham-lesion animals, adding an additional choice to the VD increased the number of VTEs and decreased the accuracy of choices. Together, these results suggest that the hippocampus may be specifically involved in VTE behavior during spatial decision making. PMID:23115549

Diffusion and Perfusion Characteristics of MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episode) in Thirteen Patients

PubMed Central

Kim, Ji Hye; Jeon, Tae Yeon; Rha, Jung Ho; Eo, Hong; Yoo, So-Young; Shu, Chang Hae

2011-01-01

Objective We analyzed the diffusion and perfusion characteristics of acute MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) lesions in a large series to investigate the controversial changes of the apparent diffusion coefficient (ADC) that were reported in prior studies. Materials and Methods We analyzed 44 newly appearing lesions during 28 stroke-like episodes in 13 patients with MELAS. We performed a visual assessment of the MR images including the ADC and perfusion maps, comparison of the ADC between the normal and abnormal areas, comparison of % ADC between the 44 MELAS lesions and the 30 acute ischemic infarcts. In addition, the patterns of evolution on follow-up MR images were analyzed. Results Decreased, increased, and normal ADCs were noted in 16 (36%), 16 (36%), and 12 (27%) lesions, respectively. The mean % ADC was 102 ± 40.9% in the MELAS and 64 ± 17.8% in the acute vascular infarcts (p < 0.001), while perfusion imaging demonstrated hyper-perfusion in six acute MELAS lesions. On follow-up images, resolution, progression, and tissue loss were noted in 10, 4, and 17 lesions, respectively. Conclusion The cytotoxic edema gradually evolves following an acute stroke-like episode in patients with MELAS, and this may overlap with hyper-perfusion and vasogenic edema. The edematous swelling may be reversible or it may evolve to encephalomalacia, suggesting irreversible damage. PMID:21228936

Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions.

PubMed

Häkkinen, T; Luoma, J S; Hiltunen, M O; Macphee, C H; Milliner, K J; Patel, L; Rice, S Q; Tew, D G; Karkola, K; Ylä-Herttuala, S

1999-12-01

We studied the expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density lipoprotein, which plays an important role in atherogenesis, generates biologically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine and oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA(2) activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytochemistry, we detected Lp-PLA(2) mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase-polymerase chain reaction analysis indicated an increased expression of Lp-PLA(2) mRNA in human atherosclerotic lesions. In addition, approximately 6-fold higher Lp-PLA(2) activity was detected in atherosclerotic aortas of Watanabe heritable hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerotic lesions express Lp-PLA(2), which could cleave any oxidatively modified phosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA(2) activity could lead to antiatherogenic effects in the vessel wall.

An unwritten anatomy lesson: The influence of Roman clothing on neuroanatomical terminology: In memoriam Albert L. Rhoton, Jr. (1932-2016).

PubMed

Turliuc, Dana Mihaela; Turliuc, Serban; Cucu, Andrei Ionut; Sava, Anca; Dumitrescu, Gabriela Florenta; Cărăuleanu, Alexandru; Buzdugă, Cătălin; Trandafir, Daniela; Costea, Claudia Florida

2016-09-01

Throughout the centuries, anatomists attempting to denominate the new structures they discovered have found inspiration in the civilization of ancient Rome and the clothing worn by its citizens. This aricle presents the origins of seven neuroanatomical terms, fimbria, velum, funiculus, lemniscus, corona, splenium, and cingulum, inspired by the clothing and jewellery of Roman women and the military attire of Roman soldiers. Thus, through their apparel, the Romans influenced the Terminologia Anatomica and "clothed" the structures of the brain and spinal cord, making them immortal. Clin. Anat. 29:685-690, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of D-cycloserine and aniracetam on spatial learning in rats with entorhinal cortex lesions.

PubMed

Zajaczkowski, W; Danysz, W

1997-01-01

A great body of behavioural and neurophysiological evidence suggests that excitatory amino acids are involved in mechanisms of learning and memory. Moreover, degeneration of glutamatergic pathways may underlie the cognitive deficits seen in various disorders such as Alzheimer's dementia. As direct stimulation of glutamatergic receptors with agonists may increase the risk of toxicity and accelerate neuropathological changes, a more valid approach seems to be positive modulation of glutamatergic receptors that may reverse the symptoms with a lower risk of excitotoxic effects. Such a possibility offered by partial agonists of the strychnine-insensitive glycine site of the NMDA receptor (Gly-B site) or positive modulators of AMPA receptors, such as aniracetam. In the present study, the effects of d-cycloserine and aniracetam were tested in two animal models of cognitive deficits (entorhinal cortex lesion-induced deficits evaluated in the radial maze and scopolamine-induced amnesia evaluated in passive avoidance test). D-cycloserine (6 mg/kg, for 10 days) had no effect on spatial working memory deficit induced by entorhinal cortex lesions. It did, however, reverse scopolamine-induced deficits in the passive avoidance test when given acutely at the same dose. In contrast, aniracetam (50 mg/kg, for 10 days) produced beneficial effects in the radial maze test in rats with entorhinal cortex lesions, but given at the same dose acutely did not influence scopolamine-induced amnesia. The positive effect of d-cycloserine against scopolamine-induced amnesia may be probably related to the cholinergic-glutamatergic interaction in the hippocampus. The negative data obtained with d-cycloserine in the model of entorhinal cortex lesions-induced cognitive deficits could be taken as a hint that it is probably not suitable for the symptomatological therapy of Alzheimer's disease. The mechanism of positive action of aniracetam cannot be explained on the basis of AMPA receptor modulation, as the dose used (50 mg/kg) is well below that required for the effect at AMPA receptors. Other actions such as peripheral effects or modulation of metabotropic receptors seem more likely.

Causal functional contributions and interactions in the attention network of the brain: an objective multi-perturbation analysis.

PubMed

Zavaglia, Melissa; Hilgetag, Claus C

2016-06-01

Spatial attention is a prime example for the distributed network functions of the brain. Lesion studies in animal models have been used to investigate intact attentional mechanisms as well as perspectives for rehabilitation in the injured brain. Here, we systematically analyzed behavioral data from cooling deactivation and permanent lesion experiments in the cat, where unilateral deactivation of the posterior parietal cortex (in the vicinity of the posterior middle suprasylvian cortex, pMS) or the superior colliculus (SC) cause a severe neglect in the contralateral hemifield. Counterintuitively, additional deactivation of structures in the opposite hemisphere reverses the deficit. Using such lesion data, we employed a game-theoretical approach, multi-perturbation Shapley value analysis (MSA), for inferring functional contributions and network interactions of bilateral pMS and SC from behavioral performance in visual attention studies. The approach provides an objective theoretical strategy for lesion inferences and allows a unique quantitative characterization of regional functional contributions and interactions on the basis of multi-perturbations. The quantitative analysis demonstrated that right posterior parietal cortex and superior colliculus made the strongest positive contributions to left-field orienting, while left brain regions had negative contributions, implying that their perturbation may reverse the effects of contralateral lesions or improve normal function. An analysis of functional modulations and interactions among the regions revealed redundant interactions (implying functional overlap) between regions within each hemisphere, and synergistic interactions between bilateral regions. To assess the reliability of the MSA method in the face of variable and incomplete input data, we performed a sensitivity analysis, investigating how much the contribution values of the four regions depended on the performance of specific configurations and on the prediction of unknown performances. The results suggest that the MSA approach is sensitive to categorical, but insensitive to gradual changes in the input data. Finally, we created a basic network model that was based on the known anatomical interactions among cortical-tectal regions and reproduced the experimentally observed behavior in visual orienting. We discuss the structural organization of the network model relative to the causal modulations identified by MSA, to aid a mechanistic understanding of the attention network of the brain.

Cerebral Amyloid Angiopathy (CAA)-Related Inflammation: Comparison of Inflammatory CAA and Amyloid-β-Related Angiitis.

PubMed

Chu, Shuguang; Xu, Feijia; Su, Ya; Chen, Hong; Cheng, Xin

2016-01-01

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a relatively rare syndrome of reversible encephalopathy and could be divided into two subtypes of inflammatory CAA (ICAA) and amyloid-β-related angiitis (ABRA) according to histopathology. We present a case of pathologically proved ABRA with partial seizures and headache, and a focal lesion in the right temporal lobes on magnetic resonance imaging. Summarized from previous 139 ABRA and ICAA cases, ABRA is preferred when the lesion is enhanced on MRI and requires combination drug therapy, while ICAA is highly suspected with ApoE genotype of ɛ4/ɛ4. More clinical markers for diagnosis of CAA-ri warrant further researches.

In vivo and in vitro evidence of somatostatin receptors expression in a dedifferentiated retroperitoneal liposarcoma.

PubMed

Imperiale, Alessio; Chenard, Marie-Pierre; Rohr, Serge; Barlier, Anne; Goichot, Bernard

2014-10-01

A 62-year-old patient presented with mildly elevated catecholamines and an abdominal painless mass. Abdominal CT revealed an 18 × 12 cm tumor in the right retroperitoneum with intense contrast enhancement. Somatostatin receptor scintigraphy (SRS) showed pathologic uptake by the lesion. Given the suspicion of paraganglioma, the patient was referred to surgery for tumor removal. Surprisingly, the histopathological examination revealed a dedifferentiated liposarcoma. Somatostatin receptors of type 2 were identified and quantified by reverse transcription polymerase chain reaction. The unexpected presentation of our patient draws clinicians' attention when performing diagnostic procedure for retroperitoneal lesions, even though hormone secretion and positive SRS strongly suggest paraganglioma.

Dental caries and pulpal disease.

PubMed

Zero, Domenick T; Zandona, Andrea Ferreira; Vail, Mychel Macapagal; Spolnik, Kenneth J

2011-01-01

This article reviews the diagnostic process, from the first clinically evident stages of the caries process to development of pulpal pathosis. The caries diagnostic process includes 4 interconnected components-staging caries lesion severity, assessing caries lesion activity, and risk assessments at the patient and tooth surface level - which modify treatment decisions for the patient. Pulpal pathosis is diagnosed as reversible pulpitis, irreversible pulpitis (asymptomatic), irreversible pulpitis (symptomatic), and pulp necrosis. Periapical disease is diagnosed as symptomatic apical periodontitis, asymptomatic apical periodontitis, acute apical abscess, and chronic apical abscess. Ultimately, the goal of any diagnosis should be to achieve better treatment decisions and health outcomes for the patient. Copyright © 2011 Elsevier Inc. All rights reserved.

West Nile Flavivirus Polioencephalomyelitis in a harbor seal (Phoca vitulina).

PubMed

Del Piero, F; Stremme, D W; Habecker, P L; Cantile, C

2006-01-01

A 12-year-old male harbor seal presented with progressive signs of neurologic dysfunction including head tremors, muzzle twitching, clonic spasms, and weakness. Lesions included polioencephalomyelitis with glial nodules, spheroids, neuronophagia, ring hemorrhages, and a few neutrophils. Neurons, fibers, and glial nodules were multifocally colonized with intracytoplasmic West Nile flavivirus antigens that were demonstrated using indirect immunohistochemical analysis. Flavivirus on cultured cells also was isolated and was identified by use of monoclonal antibodies and reverse transcriptase-polymerase chain reaction analysis. Clinical signs of disease and lesion morphology and distribution were similar to those of equine West Nile virus infection. Similar to horses, alpacas, humans, dogs, and reptiles, seals can be dead-end hosts of West Nile virus.

Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

PubMed Central

Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

2014-01-01

Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis. PMID:25101288

Inactivation of the Anterior Cingulate Cortex Impairs Extinction of Rabbit Jaw Movement Conditioning and Prevents Extinction-Related Inhibition of Hippocampal Activity

ERIC Educational Resources Information Center

Griffin, Amy L.; Berry, Stephen D.

2004-01-01

Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of…

Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation.

PubMed

Teive, H A; Brandi, I V; Camargo, C H; Bittencourt, M A; Bonfim, C M; Friedrich, M L; de Medeiros, C R; Werneck, L C; Pasquini, R

2001-09-01

Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

Reinventing the ames test as a quantitative lab that connects classical and molecular genetics.

PubMed

Goodson-Gregg, Nathan; De Stasio, Elizabeth A

2009-01-01

While many institutions use a version of the Ames test in the undergraduate genetics laboratory, students typically are not exposed to techniques or procedures beyond qualitative analysis of phenotypic reversion, thereby seriously limiting the scope of learning. We have extended the Ames test to include both quantitative analysis of reversion frequency and molecular analysis of revertant gene sequences. By giving students a role in designing their quantitative methods and analyses, students practice and apply quantitative skills. To help students connect classical and molecular genetic concepts and techniques, we report here procedures for characterizing the molecular lesions that confer a revertant phenotype. We suggest undertaking reversion of both missense and frameshift mutants to allow a more sophisticated molecular genetic analysis. These modifications and additions broaden the educational content of the traditional Ames test teaching laboratory, while simultaneously enhancing students' skills in experimental design, quantitative analysis, and data interpretation.

Sex Difference in the Morphology of Pineal Gland in Adults Based on Brain Magnetic Resonance Imaging.

PubMed

Han, Qing; Li, Youqiong; Wang, Jincheng; Zhao, Xue

2018-03-30

We aimed to figure out the anatomical features of pineal gland region on magnetic resonance imaging (MRI) and to explore the sex difference in pineal gland-related parameters with increasing age. We measured the pineal gland on MRI images from 198 healthy adults (96 males and 102 females). Included subjects were divided into 4 age groups. After 3-dimensional reconstruction, the anatomic features of pineal gland and its distances to superior colliculus and splenium of corpus callosum were analyzed in each group. The prevalence of cystic pineal gland was calculated. Moreover, we calculated the volume of pineal gland (PGV) and explored the differences of PGV in males and females across different age groups. Linear regression analysis was performed to detect the relationship between age and pineal gland-related parameters. In 198 subjects, the mean length, width, and height of pineal gland were 7.58 ± 0.45 mm, 4.92 ± 0.40 mm, and 2.90 ± 0.20 mm. The distances between pineal gland and superior colliculus as well as splenium of corpus callosum were 3.96 ± 0.92 mm and 4.3 ± 1.89 mm, respectively. The PGV was 54.1 ± 7.02 mm. Significant sex differences were found in pineal gland length (P < 0.001), cranial cavity diameter (P < 0.001), pineal gland index (P < 0.001) and PGV values (P = 0.02). The prevalence of cystic pineal gland was 36.4% in total subjects, 41.7% in males and 32.4% in females. No linear relationship was found between age and pineal gland parameters. We measured the pineal gland morphology based on MRI images. Significant influences on pineal gland parameters were found in subjects with different sex, whereas no effect was observed from age.

Analysis of the contribution of experimental bias, experimental noise, and inter-subject biological variability on the assessment of developmental trajectories in diffusion MRI studies of the brain.

PubMed

Sadeghi, Neda; Nayak, Amritha; Walker, Lindsay; Okan Irfanoglu, M; Albert, Paul S; Pierpaoli, Carlo

2015-04-01

Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and mean diffusivity (MD) have been used in many studies of postnatal brain development. A common finding of previous studies is that these tensor-derived measures vary widely even in healthy populations. This variability can be due to inherent inter-individual biological differences as well as experimental noise. Moreover, when comparing different studies, additional variability can be introduced by different acquisition protocols. In this study we examined scans of 61 individuals (aged 4-22 years) from the NIH MRI study of normal brain development. Two scans were collected with different protocols (low and high resolution). Our goal was to separate the contributions of biological variability and experimental noise to the overall measured variance, as well as to assess potential systematic effects related to the use of different protocols. We analyzed FA and MD in seventeen regions of interest. We found that biological variability for both FA and MD varies widely across brain regions; biological variability is highest for FA in the lateral part of the splenium and body of the corpus callosum along with the cingulum and the superior longitudinal fasciculus, and for MD in the optic radiations and the lateral part of the splenium. These regions with high inter-individual biological variability are the most likely candidates for assessing genetic and environmental effects in the developing brain. With respect to protocol-related effects, the lower resolution acquisition resulted in higher MD and lower FA values for the majority of regions compared with the higher resolution protocol. However, the majority of the regions did not show any age-protocol interaction, indicating similar trajectories were obtained irrespective of the protocol used. Published by Elsevier Inc.

Improved animal models for testing gene therapy for atherosclerosis.

PubMed

Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

2014-04-01

Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long-term therapy from vascular endothelium without accelerating atherosclerotic disease.

Reversion to virulence and efficacy of an attenuated Canarypox vaccine in Hawai'i 'Amakihi (Hemignathus virens).

PubMed

Atkinson, Carter T; Wiegand, Kimberly C; Triglia, Dennis; Jarvi, Susan I

2012-12-01

Vaccines may be effective tools for protecting small populations of highly susceptible endangered, captive-reared, or translocated Hawaiian honeycreepers from introduced Avipoxvirus, but their efficacy has not been evaluated. An attenuated Canarypox vaccine that is genetically similar to one of two passerine Avipoxvirus isolates from Hawai'i and distinct from Fowlpox was tested to evaluate whether Hawai'i 'Amakihi (Hemignathus virens) can be protected from wild isolates of Avipoxvirus from the Hawaiian Islands. Thirty-one (31) Hawai'i 'Amakihi were collected from high-elevation habitats on Mauna Kea Volcano, where pox transmission is rare, and randomly divided into two groups. One group was vaccinated with Poximune C, whereas the other group received a sham vaccination with sterile water. Four of 15 (27%) vaccinated birds developed life-threatening disseminated lesions or lesions of unusually long duration, whereas one bird never developed a vaccine-associated lesion or "take." After vaccine lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox (FP) from Hawai'i, a Hawai'i 'Amakihi isolate of a Canarypox-like virus (PV1), or a Hawai'i 'Amakihi isolate of a related, but distinct, passerine Avipoxvirus (PV2). Similarly, three random groups of five unvaccinated 'Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated 'Amakihi challenged with FP had transient infections with no clinical signs of infection. Mortality in vaccinated 'Amakihi challenged with PV1 and PV2 ranged from 0% (0/5) for PV1 to 60% (3/5) for PV2. Mortality in unvaccinated 'Amakihi ranged from 40% (2/5) for PV1 to 100% (5/5) for PV2. Although the vaccine provided some protection against PV1, both potential for vaccine reversion and low efficacy against PV2 preclude its use in captive or wild honeycreepers.

Reversion to virulence and efficacy of an attenuated canarypox vaccine in Hawai'i 'Amakihi (Hemignathus Virens)

USGS Publications Warehouse

Atkinson, Carter T.; Wiegand, Kimberly C.; Triglia, Dennis; Jarvi, Susan I.

2012-01-01

Vaccines may be effective tools for protecting small populations of highly susceptible endangered, captive-reared, or translocated Hawaiian honeycreepers from introduced Avipoxvirus, but their efficacy has not been evaluated. An attenuated Canarypox vaccine that is genetically similar to one of two passerine Avipoxvirus isolates from Hawai‘i and distinct from Fowlpox was tested to evaluate whether Hawai‘i ‘Amakihi (Hemignathus virens) can be protected from wild isolates of Avipoxvirus from the Hawaiian Islands. Thirty-one (31) Hawai‘i ‘Amakihi were collected from high-elevation habitats on Mauna Kea Volcano, where pox transmission is rare, and randomly divided into two groups. One group was vaccinated with Poximune C®, whereas the other group received a sham vaccination with sterile water. Four of 15 (27%) vaccinated birds developed life-threatening disseminated lesions or lesions of unusually long duration, whereas one bird never developed a vaccine-associated lesion or “take.” After vaccine lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox (FP) from Hawai‘i, a Hawai‘i ‘Amakihi isolate of a Canarypox-like virus (PV1), or a Hawai‘i ‘Amakihi isolate of a related, but distinct, passerine Avipoxvirus (PV2). Similarly, three random groups of five unvaccinated ‘Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated ‘Amakihi challenged with FP had transient infections with no clinical signs of infection. Mortality in vaccinated ‘Amakihi challenged with PV1 and PV2 ranged from 0% (0/5) for PV1 to 60% (3/5) for PV2. Mortality in unvaccinated ‘Amakihi ranged from 40% (2/5) for PV1 to 100% (5/5) for PV2. Although the vaccine provided some protection against PV1, both potential for vaccine reversion and low efficacy against PV2 preclude its use in captive or wild honeycreepers.

Identification of G-quadruplex forming sequences in three manatee papillomaviruses

PubMed Central

Zahin, Maryam; Dean, William L.; Ghim, Shin-je; Joh, Joongho; Gray, Robert D.; Khanal, Sujita; Bossart, Gregory D.; Mignucci-Giannoni, Antonio A.; Rouchka, Eric C.; Jenson, Alfred B.; Trent, John O.; Chaires, Jonathan B.

2018-01-01

The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs. PMID:29630682

Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats.

PubMed

Stancic-Rokotov, D; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Staresinic, M; Gjurasin, M; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Sikiric, P; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Kokic, N; Jagic, V; Boban-Blagaic, A

2001-01-01

Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.

Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.

PubMed

Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Vrcic, Hrvoje; Sebecic, Bozidar

2011-01-01

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, safe in inflammatory bowel disease clinical trials (GEPPPGKPADDAGLV, M.W. 1419, PL 14736) and wound healing, stable in human gastric juice and has no reported toxicity. We focused on BPC 157 as a therapy in peridontitis, esophagus, stomach, duodenum, intestine, liver and pancreas lesions. Particularly, it has a prominent effect on alcohol-lesions (i.e., acute, chronic) and NSAIDs-lesions (interestingly, BPC 157 both prevents and reverses adjuvant arthritis). In rat esophagitis and failed function of both lower esophageal sphincter (LES) and pyloric sphincters (PS), BPC 157 increased pressure in both sphincters till normal and reduced esophagitis. However, in healthy rats, it may decrease (PS) or increase (LES) the pressure in sphincters. It has strong angiogenic potential, it acts protectively on endothelium, prevents and reverses thrombus formation after abdominal aorta anastomosis, affects many central disturbances (i.e., dopamine and 5-HT system), the NO-system (either L-arginine and L-NAME effects), endothelin, acts as a free radical scavenger (counteracting CCl4-, paracetamol-, diclofenac-injuries) and exhibits neuroprotective properties. BPC 157 successfully heals the intestinal anastomosis, gastrocutaneous, duodenocutaneous and colocutaneous fistulas in rats, as well as interacting with the NO-system. Interestingly, the fistula closure was achieved even when the BPC 157 therapy was postponed for one month. In short-bowel syndrome escalating throughout 4 weeks, the constant weight gain above preoperative values started immediately with peroral and parental BPC 157 therapy and the villus height, crypth depth and muscle thickness (inner (circular) muscular layer) additionally increased. Thus, BPC 157 may improve gastrointestinal tract therapy.

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease.

PubMed

Padel, Thomas; Özen, Ilknur; Boix, Jordi; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

2016-10-01

Parkinson's disease (PD) is a neurodegenerative disease where the degeneration of the nigrostriatal pathway leads to specific motor deficits. There is an unmet medical need for regenerative treatments that stop or reverse disease progression. Several growth factors have been investigated in clinical trials to restore the dopaminergic nigrostriatal pathway damaged in PD. Platelet-derived growth factor-BB (PDGF-BB), a molecule that recruits pericytes to stabilize microvessels, was recently investigated in a phase-1 clinical trial, showing a dose-dependent increase in dopamine transporter binding in the putamen of PD patients. Interestingly, evidence is accumulating that PD is paralleled by microvascular changes, however, whether PDGF-BB modifies pericytes in PD is not known. Using a pericyte reporter mouse strain, we investigate the functional and restorative effect of PDGF-BB in a partial 6-hydroxydopamine medial forebrain bundle lesion mouse model of PD, and whether this restorative effect is accompanied by changes in pericyte features. We demonstrate that a 2-week treatment with PDGF-BB leads to behavioural recovery using several behavioural tests, and partially restores the nigrostriatal pathway. Interestingly, we find that pericytes are activated in the striatum of PD lesioned mice and that these changes are reversed by PDGF-BB treatment. The modulation of brain pericytes may contribute to the PDGF-BB-induced neurorestorative effects, PDGF-BB allowing for vascular stabilization in PD. Pericytes might be a new cell target of interest for future regenerative therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

PubMed

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

Salivary enhancement: current status and future therapies.

PubMed

Atkinson, J C; Baum, B J

2001-10-01

Saliva provides the principal protective milieu for teeth by modulating oral microbial ecosystems and reversing the initial phases of caries development. Patients with inadequate salivary function are at increased risk for dental decay. Therefore, it is likely that therapies that increase overall fluid output of these individuals will reverse early carious lesions. The most common causes of salivary dysfunction are medication usage, Sjögren's syndrome, and damage of salivary parenchyma during therapeutic irradiation. For patients with remaining functional acinar tissue, treatment with the parasypathomimetic secretogogues pilocarpine and Cevimeline may provide relief. However, these medications do not benefit all patients. The possibilities of using gene therapy and tissue engineering to develop treatments for those with severe salivary dysfunction are discussed.

Lesions to right posterior parietal cortex impair visual depth perception from disparity but not motion cues

PubMed Central

Leopold, David A.; Humphreys, Glyn W.; Welchman, Andrew E.

2016-01-01

The posterior parietal cortex (PPC) is understood to be active when observers perceive three-dimensional (3D) structure. However, it is not clear how central this activity is in the construction of 3D spatial representations. Here, we examine whether PPC is essential for two aspects of visual depth perception by testing patients with lesions affecting this region. First, we measured subjects' ability to discriminate depth structure in various 3D surfaces and objects using binocular disparity. Patients with lesions to right PPC (N = 3) exhibited marked perceptual deficits on these tasks, whereas those with left hemisphere lesions (N = 2) were able to reliably discriminate depth as accurately as control subjects. Second, we presented an ambiguous 3D stimulus defined by structure from motion to determine whether PPC lesions influence the rate of bistable perceptual alternations. Patients' percept durations for the 3D stimulus were generally within a normal range, although the two patients with bilateral PPC lesions showed the fastest perceptual alternation rates in our sample. Intermittent stimulus presentation reduced the reversal rate similarly across subjects. Together, the results suggest that PPC plays a causal role in both inferring and maintaining the perception of 3D structure with stereopsis supported primarily by the right hemisphere, but do not lend support to the view that PPC is a critical contributor to bistable perceptual alternations. This article is part of the themed issue ‘Vision in our three-dimensional world’. PMID:27269606

[Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

PubMed

Voigt-Zimmermann, S; Arens, C

2014-12-01

In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

Duplex Interrogation by a Direct DNA Repair Protein in Search of Base Damage

PubMed Central

Yi, Chengqi; Chen, Baoen; Qi, Bo; Zhang, Wen; Jia, Guifang; Zhang, Liang; Li, Charles J.; Dinner, Aaron R.; Yang, Cai-Guang; He, Chuan

2012-01-01

ALKBH2 is a direct DNA repair dioxygenase guarding mammalian genome against N1-methyladenine, N3-methylcytosine, and 1,N6-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 displays two novel features: i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability; ii) ALKBH2 does not have nor need a “damage-checking site”, which is critical for preventing spurious base-cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly. PMID:22659876

Reversal of primary root caries lesions after daily intake of milk supplemented with fluoride and probiotic lactobacilli in older adults.

PubMed

Petersson, Lars G; Magnusson, Kerstin; Hakestam, Ulf; Baigi, Amir; Twetman, Svante

2011-11-01

To evaluate the effect of milk supplemented with fluoride and/or probiotic bacteria on primary root caries lesions (PRCL) in older adults. After informed consent, 160 healthy subjects, 58-84 years of age, with at least two PRCL were recruited and randomly assigned to one of four parallel study groups drinking 200 ml milk once daily for 15 months. Group A consumed standard milk (placebo); Group B ingested milk supplemented with 5 ppm F and probiotic bacteria (Lactobacillus rhamnosus LB21, 10(7) CFU/mL); Group C drank milk with only probiotic bacteria and group D milk contained only fluoride. Primary endpoints were Root Caries Index (RCI) and electric resistance measurements (ECM) carried out by one blinded single examiner. Secondary endpoints were mutans streptococci and lactobacilli counts in saliva and plaque estimated with chair-side tests. Data were compared within and between groups with non-parametric tests. The drop out rate was 38%. At baseline there were no statistical differences between the groups. Significantly higher numbers of RCI reversals were found in groups B, C and D compared with group A (p < 0.05). The mean ECM values increased significantly (p < 0.05) in all groups except for the placebo group A, indicating that remineralization occurred. The effect was most beneficial in the two groups that contained fluoride. No significant alterations were displayed regarding the microbial counts. No severe adverse effects were reported during intervention. Daily intake of milk supplemented with fluoride and/or probiotic bacteria may reverse soft and leathery PRCL in older adults.

Carotid artery stenting: current and emerging options

PubMed Central

Morr, Simon; Lin, Ning; Siddiqui, Adnan H

2014-01-01

Carotid artery stenting technologies are rapidly evolving. Options for endovascular surgeons and interventionists who treat occlusive carotid disease continue to expand. We here present an update and overview of carotid stenting devices. Evidence supporting carotid stenting includes randomized controlled trials that compare endovascular stenting to open surgical endarterectomy. Carotid technologies addressed include the carotid stents themselves as well as adjunct neuroprotective devices. Aspects of stent technology include bare-metal versus covered stents, stent tapering, and free-cell area. Drug-eluting and cutting balloon indications are described. Embolization protection options and new direct carotid access strategies are reviewed. Adjunct technologies, such as intravascular ultrasound imaging and risk stratification algorithms, are discussed. Bare-metal and covered stents provide unique advantages and disadvantages. Stent tapering may allow for a more fitted contour to the caliber decrement between the common carotid and internal carotid arteries but also introduces new technical challenges. Studies regarding free-cell area are conflicting with respect to benefits and associated risk; clinical relevance of associated adverse effects associated with either type is unclear. Embolization protection strategies include distal filter protection and flow reversal. Though flow reversal was initially met with some skepticism, it has gained wider acceptance and may provide the advantage of not crossing the carotid lesion before protection is established. New direct carotid access techniques address difficult anatomy and incorporate sophisticated flow-reversal embolization protection techniques. Carotid stenting is a new and exciting field with rapidly advancing technologies. Embolization protection, low-risk deployment, and lesion assessment and stratification are active areas of research. Ample room remains for further innovations and developments. PMID:25349483

An object-based approach for detecting small brain lesions: application to Virchow-Robin spaces.

PubMed

Descombes, Xavier; Kruggel, Frithjof; Wollny, Gert; Gertz, Hermann Josef

2004-02-01

This paper is concerned with the detection of multiple small brain lesions from magnetic resonance imaging (MRI) data. A model based on the marked point process framework is designed to detect Virchow-Robin spaces (VRSs). These tubular shaped spaces are due to retraction of the brain parenchyma from its supplying arteries. VRS are described by simple geometrical objects that are introduced as small tubular structures. Their radiometric properties are embedded in a data term. A prior model includes interactions describing the clustering property of VRS. A Reversible Jump Markov Chain Monte Carlo algorithm (RJMCMC) optimizes the proposed model, obtained by multiplying the prior and the data model. Example results are shown on T1-weighted MRI datasets of elderly subjects.

Testing of Experimental Compounds for Efficacy against Leishmania

DTIC Science & Technology

1990-02-28

donovani WR06026’ RA 1 • 06 13 chemotherapy- berberine pyrimidine nucleotides, 06 20 golden hamster: Sinefungin, 19. ABSTRACT (Continue on reverse if...equivalent when administered either orally or via the intramuscular route. In other special studies the quaternary alkaloid, berberine , and three of its...hamsters and berberine and one derivative (8-cyanodihydroberberine) produced 56% and 46% suppression of cutaneous lesion areas respectively in hamsters

Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

PubMed

Singhi, Pratibha; Saini, Arushi Gahlot; Sankhyan, Naveen; Gupta, Pankaj; Vyas, Sameer

2015-01-01

A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. © The Author(s) 2014.

Treatment of The Posterior Unstable Shoulder

PubMed Central

Alepuz, Eduardo Sánchez

2017-01-01

Background: It is estimated that approximately 5% of glenohumeral instabilities are posterior. There are a number of controversies regarding therapeutic approaches for these patients. Methods: We analyse the main surgery alternatives for the treatment of the posterior shoulder instability. We did a research of the publications related with posterior glenohumeral instability. Results: There are conservative and surgical treatment options. Conservative treatment has positive results in most patients, with around 65 to 80% of cases showing recurrent posterior dislocation. There are multiple surgical techniques, both open and arthroscopic, for the treatment of posterior glenohumeral instability. There are procedures that aim to repair bone defects and others that aim to repair soft tissues and capsulolabral injuries. The treatment should be planned according to each case on an individual basis according to the patient characteristics and the injury type. Surgical treatment is indicated in patients with functional limitations arising from instability and/or pain that have not improved with rehabilitation treatment. The indications for arthroscopic treatment are recurrent posterior subluxation caused by injury of the labrum or the capsulolabral complex; recurrent posterior subluxation caused by capsuloligamentous laxity or capsular redundancy; and multidirectional instability with posterior instability as a primary component. Arthroscopic assessment will help identify potential injuries associated with posterior instability such as bone lesions or defects and lesions or defects of soft tissues. The main indications for open surgery would be in cases of Hill Sachs lesions or broad reverse Bankart lesions not accessible by arthroscopy. We indicated non-anatomical techniques (McLaughlin or its modifications) for reverse Hill-Sachs lesions with impairment of the articular surface between 20% and 50%. Disimpaction of the fracture and placement of bone graft (allograft or autograft) is a suitable treatment for acute lesions that do not exceed 50% of the articular surface and with articular cartilage in good condition. Reconstruction with allograft may be useful in lesions affecting up to 50% of the humeral surface and should be considered when there is a situation of non-viable cartilage at the fracture site. For defects greater than 50% of the articular surface or in the case of dislocations over 6 months in duration where there is poor bone quality, some authors advocate substitution techniques as a treatment of choice. The main techniques for treating glenoid bone defects are posterior bone block and posterior opening osteotomy of the glenoid. Conclusions: The treatment of the posterior glenohumeral instability has to be individualized based on the patient´s injuries, medical history, clinical exam and goals. The most important complications in the treatment of posterior glenohumeral instability are recurrent instability, avascular necrosis and osteoarthritis. PMID:28979596

Fronto-temporal white matter connectivity predicts reversal learning errors

PubMed Central

Alm, Kylie H.; Rolheiser, Tyler; Mohamed, Feroze B.; Olson, Ingrid R.

2015-01-01

Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus–outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex. PMID:26150776

Chorioretinal Lesions Presumed Secondary to Zika Virus Infection in an Immunocompromised Adult.

PubMed

Henry, Christopher R; Al-Attar, Luma; Cruz-Chacón, Alexis M; Davis, Janet L

2017-04-01

Zika virus has spread rapidly throughout the Americas since 2015. The public health implications of Zika virus infection lend special importance to identifying the virus in unsuspected hosts. To describe relevant imaging studies and clinical features of chorioretinal lesions that are presumably associated with Zika virus and that share analogous features with chorioretinal lesions reported in cases of Dengue fever and West Nile virus. This is a case report from an academic referral center in Miami, Florida, of a woman in her 60s from Guaynabo, Puerto Rico, who presented with reduced visual acuity and bilateral diffuse, subretinal, confluent, placoid, and multifocal chorioretinal lesions. The patient was observed over a 5-month period. Visual acuity, clinical course, and multimodal imaging study results. Fluorescein angiography revealed early hypofluorescence and late staining of the chorioretinal lesions. Optical coherence tomography demonstrated outer retinal disruption in the placoid macular lesions. Zika RNA was detected in a plasma sample by real-time reverse transcription polymerase chain reaction testing and was suspected to be the cause of chorioretinal lesions after other viral and infectious causes were ruled out. Three weeks after the onset of symptoms, the patient's visual acuity had improved to 20/60 OD and 20/25 OS, with intraocular pressures of 18 mm Hg OD and 19 mm Hg OS. In 6 weeks, the chorioretinal lesions had healed and visual acuity had improved to 20/25 OD and 20/20 OS. Follow-up optical coherence tomography demonstrated interval recovery of the outer retina and photoreceptors. Acute-onset, self-resolving, placoid, or multifocal nonnecrotizing chorioretinal lesions may be a feature of active Zika virus chorioretinitis, as reported in other Flavivirus infections in adults. Similar findings in potentially exposed adults suggest that clinicians should consider IgM antibody or polymerase chain reaction testing for Zika virus as well as diagnostic testing for Dengue fever and West Nile virus.

Contrast enhancement of central nervous system lesions: multicenter intraindividual crossover comparative study of two MR contrast agents.

PubMed

Maravilla, Kenneth R; Maldjian, Joseph A; Schmalfuss, Ilona M; Kuhn, Matthew J; Bowen, Brian C; Wippold, Franz J; Runge, Val M; Knopp, Michael V; Kremer, Stephane; Wolansky, Leo J; Anzalone, Nicoletta; Essig, Marco; Gustafsson, Lars

2006-08-01

To prospectively compare gadobenate dimeglumine with gadopentetate dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance (MR) imaging of central nervous system (CNS) lesions. This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test. Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P < .0001). Significant (P < .0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P < .001) in patients with intraaxial and extraaxial lesions. Gadobenate compared with gadopentetate at an equivalent dose provides significantly better enhancement and diagnostic information for CNS MR imaging. RSNA, 2006

Cholecystokinin receptor antagonist halts progression of pancreatic cancer precursor lesions and fibrosis in mice.

PubMed

Smith, Jill P; Cooper, Timothy K; McGovern, Christopher O; Gilius, Evan L; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A; Gutkind, J Silvio; Matters, Gail L

2014-10-01

Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved in the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-Kras transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK receptor antagonist (proglumide, 0.1 mg/mL). Pancreas from the mice were removed and examined histologically for number and grade of PanINs after 1, 2, or 4 months of antagonist therapy. Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed, and progression to advanced lesions arrested in mice treated with proglumide compared with the controls (P = 0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared with vehicle (P < 0.001). These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. The use of CCK receptor antagonists may have a role in cancer prophylaxis in high-risk subjects and may reduce fibrosis in the microenvironment.

CHOLECYSTOKININ RECEPTOR ANTAGONIST HALTS PROGRESSION OF PANCREATIC CANCER PRECURSOR LESIONS AND FIBROSIS IN MICE

PubMed Central

Smith, Jill P.; Cooper, Timothy K.; McGovern, Christopher O.; Gilius, Evan L.; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A.; Gutkind, J. Silvio; Matters, Gail L.

2014-01-01

Objectives Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved with the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. Methods The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-KrasG12D transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK-receptor antagonist (proglumide, 0.1mg/ml). Pancreas from mice were removed and examined histologically for number and grade of PanINs after 1, 2 or 4 months of antagonist therapy. Results Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed and progression to advanced lesions arrested in mice treated with proglumide compared to controls (p=0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared to vehicle (pitalic>0.001). Conclusions These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. Use of CCK-receptor antagonists may have a role in cancer prophylaxis in high risk subjects, and may reduce fibrosis in the microenvironment. PMID:25058882

Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination

PubMed Central

Guglielmetti, C.; Veraart, J.; Roelant, E.; Mai, Z.; Daans, J.; Van Audekerke, J.; Naeyaert, M.; Vanhoutte, G.; Delgado y Palacios, R.; Praet, J.; Fieremans, E.; Ponsaerts, P.; Sijbers, J.; Van der Linden, A.; Verhoye, M.

2016-01-01

Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, MK, RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stage of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event. PMID:26525654

Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression.

PubMed

Amaya, Ronny; Cancel, Limary M; Tarbell, John M

2016-01-01

Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle-SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease.

Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression

PubMed Central

Amaya, Ronny; Cancel, Limary M.; Tarbell, John M.

2016-01-01

Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle–SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease. PMID:27846267

Prevalence and activity of Epstein-Barr virus and human cytomegalovirus in symptomatic and asymptomatic apical periodontitis lesions.

PubMed

Hernádi, Katinka; Szalmás, Anita; Mogyorósi, Richárd; Czompa, Levente; Veress, György; Csoma, Eszter; Márton, Ildikó; Kónya, József

2010-09-01

Apical periodontitis is a polymicrobial inflammation with a dominant flora of opportunistic Gram-negative bacteria; however, a pathogenic role of human herpesviruses such as Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) has been implicated recently. The aims of this study were to determine the prevalence, activity, and disease association of EBV and HCMV in apical periodontitis in an Eastern Hungarian population. Forty samples with apical periodontitis (17 symptomatic and 23 asymptomatic) and 40 healthy pulp controls were collected. EBV and HCMV prevalences were measured by polymerase chain reaction (PCR) detection of the viral DNA and viral activity was tested by reverse-transcription PCR amplification of viral messenger RNA. EBV DNA and EBNA-2 messenger RNA were found in apical periodontitis lesions at significantly (p < 0.0001) higher frequencies (72.5% and 50%, respectively) than in controls (both 2.5%). The occurrence of HCMV infection was rare in both apical lesions (10%) and controls (0%). The presence of EBV DNA in apical lesions was associated significantly with large (> or = 5 mm) lesion size (p = 0.02) but not with symptoms (p = 0.30). Symptomatic manifestation was significantly associated with the co-occurrence (odds ratio [OR], 8.80; 95% confidence interval [CI], 1.69-45.76) but not the sole occurrences of EBNA-2 messenger RNA (OR, 2.29; 95% CI, 0.48-11.06) and large lesion size (OR, 4.02; 95% CI, 0.81-19.89). EBV infection is a frequent event in apical periodontitis, whereas the involvement of HCMV still remains to be elucidated. This study showed that symptomatic manifestation was likely to occur if a large-sized apical periodontitis lesion is aggravated with active EBV infection. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Mapping 3D breast lesions from full-field digital mammograms using subject-specific finite element models

NASA Astrophysics Data System (ADS)

García, E.; Oliver, A.; Diaz, O.; Diez, Y.; Gubern-Mérida, A.; Martí, R.; Martí, J.

2017-03-01

Patient-specific finite element (FE) models of the breast have received increasing attention due to the potential capability of fusing images from different modalities. During the Magnetic Resonance Imaging (MRI) to X-ray mammography registration procedure, the FE model is compressed mimicking the mammographic acquisition. Subsequently, suspicious lesions in the MRI volume can be projected into the 2D mammographic space. However, most registration algorithms do not provide the reverse information, avoiding to obtain the 3D geometrical information from the lesions localized in the mammograms. In this work we introduce a fast method to localize the 3D position of the lesion within the MRI, using both cranio-caudal (CC) and medio-lateral oblique (MLO) mammographic projections, indexing the tetrahedral elements of the biomechanical model by means of an uniform grid. For each marked lesion in the Full-Field Digital Mammogram (FFDM), the X-ray path from source to the marker is calculated. Barycentric coordinates are computed in the tetrahedrons traversed by the ray. The list of elements and coordinates allows to localize two curves within the MRI and the closest point between both curves is taken as the 3D position of the lesion. The registration errors obtained in the mammographic space are 9.89 +/- 3.72 mm in CC- and 8.04 +/- 4.68 mm in MLO-projection and the error in the 3D MRI space is equal to 10.29 +/- 3.99 mm. Regarding the uniform grid, it is computed spending between 0.1 and 0.7 seconds. The average time spent to compute the 3D location of a lesion is about 8 ms.

Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

PubMed

Lane, E L; Cheetham, S; Jenner, P

2008-01-01

The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

PubMed

Vergara-Aragón, Patricia; Domínguez-Marrufo, Leonardo Eduardo; Ibarra-Guerrero, Patricia; Hernandez-Ramírez, Heidi; Hernández-Téllez, Beatriz; López-Martínez, Irma Elena; Sánchez-Cervantes, Ivonne; Santiago-Jacinto, Patricia; García-Macedo, Jorge Alberto; Valverde-Aguilar, Guadalupe; Santiago, Julio

2011-01-01

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

[Isolated severe neurologic disorders in post-partum: posterior reversible encephalopathy syndrome].

PubMed

Wernet, A; Benayoun, L; Yver, C; Bruno, O; Mantz, J

2007-01-01

Just after Caesarean section for twin pregnancy and feto-pelvic dysproportion, a woman presented severe headaches and arterial hypertension, then blurred vision, then generalised seizures. There were no oedematous syndrome, proteinuria was negative, ASAT were 1.5 N and platelet count was 120,000/mm(3). Cerebral CT-scan was normal. Posterior reversible encephalopathy syndrome (PRES) was diagnosed on MRI. A second MRI performed at day 9 showed complete regression of cerebral lesions, while patient was taking anti-hypertensive and antiepileptic drugs. PRES has to be evoked in post-partum central neurological symptoms, even in absence of classical sign of pre-eclampsia, like proteinuria. PRES and eclampsia share probably common physiopathological pathways. There management and prognosis seems identical.

Targeting mrtl to Reverse Myc in Breast Oncogenesis

DTIC Science & Technology

2011-06-01

overlying skin , perineural invasion, lymphovascular invasion, 1/14 lymph nodes positive metastatic carcinoma with extranodal extension, 2.5 cm pT4b...successfully acquired an additional 8 primary invasive breast carcinoma specimens, 1 metastatic lesion of breast tumor origin, 3 adjacent uninvolved...Her2-neu-positive, lobular features, 21 cm, modified Bloom-Richardson grade III/III, ypT3; N2. metastatic carcinoma involving 4/11 lymph nodes

Interposition vein graft for giant coronary aneurysm repair

NASA Technical Reports Server (NTRS)

Firstenberg, M. S.; Azoury, F.; Lytle, B. W.; Thomas, J. D.

2000-01-01

Coronary aneurysms in adults are rare. Surgical treatment is often concomitant to treating obstructing coronary lesions. However, the ideal treatment strategy is poorly defined. We present a case of successful treatment of a large coronary artery aneurysm with a reverse saphenous interposition vein graft. This modality offers important benefits over other current surgical and percutaneous techniques and should be considered as an option for patients requiring treatment for coronary aneurysms.

MicroRNAs for Detection of Pancreatic Neoplasia

PubMed Central

Vila-Navarro, Elena; Vila-Casadesús, Maria; Moreira, Leticia; Duran-Sanchon, Saray; Sinha, Rupal; Ginés, Àngels; Fernández-Esparrach, Glòria; Miquel, Rosa; Cuatrecasas, Miriam; Castells, Antoni; Lozano, Juan José; Gironella, Meritxell

2017-01-01

Objective: The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia. Objective: Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates. Methods: Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1—52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2—95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C). Results: In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively. Conclusions: miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer. PMID:27232245

Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions

PubMed Central

Mallery, Susan R.; Zwick, Jared C.; Pei, Ping; Tong, Meng; Larsen, Peter E.; Shumway, Brian S.; Lu, Bo; Fields, Henry W.; Mumper, Russell J.; Stoner, Gary D.

2010-01-01

Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation. PMID:18559542

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice

PubMed Central

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-01-01

Background and Purpose Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Experimental Approach Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Key Results Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (−70%) and secretion (−28%) by peritoneal macrophages. Conclusions and Implications Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. PMID:25572138

Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).

PubMed

Kaneko, Ryosuke; Sato, Atsuko; Hamada, Shun; Yagi, Takeshi; Ohsawa, Ichiro; Ohtsuki, Mamitaro; Kobayashi, Eiji; Hirabayashi, Masumi; Murakami, Takashi

2016-08-01

Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis.

Fenretinide

PubMed Central

Pavone, Mary Ellen; Malpani, Saurabh S.; Dyson, Matthew; Kim, J. Julie; Bulun, Serdar E.

2016-01-01

Objective: Fenretinide is a synthetic retinoid analogue that promotes apoptosis but has decreased toxicity when compared to other retinoids. We have previously shown that retinoic acid (RA) production in endometriotic tissue is decreased, resulting in reduced estrogen metabolism and apoptotic resistance. We hypothesize fenretinide may induce apoptosis in endometriotic cells and tissues, thereby reducing disease burden. Materials and Methods: Primary endometriotic stromal cells were collected, isolated, cultured, and treated with fenretinide in doses from 0 to 20 µmol/L. Cell count, viability, and immunoblots were performed to examine apoptosis. Quantitative reverse transcription-polymerase chain reaction from endometriotic cells treated with fenretinide was used to examine expression of genes involved in RA signaling including stimulated by RA 6 (STRA6), cellular RA binding protein 2 (CRABP2), and fatty acid binding protein 5 (FABP5). Endometriotic tissue was xenografted subcutaneously into the flanks of mice which were treated with fenretinide for 2 weeks, after which the mice were killed and lesion volumes calculated. Statistical analysis was performed using t test and analysis of variance. Results: Treatment with fenretinide significantly decreased total cell count (doses 5-20 µL) and viability (doses 10-20 µmol/L). Fenretinide increased protein levels of the apoptotic marker poly (ADP ribose) polymerase (starting at 10 µmol/L) and decreased proliferation marker proliferating cell nuclear antigen (10 µmol/L, starting at 8-day treatment). Examination of genes involved in retinoid uptake and action showed that treatment induced STRA6 expression while expression of CRABP2 and FABP5 remained unchanged. Fenretinide also significantly decreased the endometriotic lesion xenograft volume. Conclusions: Fenretinide increases STRA6 expression thereby potentially reversing the pathological loss of retinoid availability. Treatment with this compound induces apoptosis. In vivo treatments decrease lesion volume. Targeting the RA signaling pathway may be a promising novel treatment for women with endometriosis. PMID:26919975

Cykotine mRNA expression in mouse retina after laser injury by reverse transcriptase-polymerase chain reaction (RT-PCR)

NASA Astrophysics Data System (ADS)

Schuschereba, Steven T.; Bowman, Phillip D.; Ujimore, Veronica; Hoxie, Stephen W.; Pizarro, Jose M.; Cross, Michael E.; Lund, David J.

1996-04-01

The purpose of this study was to identify cytokines produced by the retina after laser injury. With the aid of a scanning laser ophthalmoscope (SLO), right eyes of mice received lesions from a continuous wave argon laser. Left eyes served as unirradiated controls. At 2, 4, 6, 12, 24, and 48 hr after laser irradiation groups of 3 mice were euthanized and retinas fixed for histology or isolated for RNA. Messenger RNA (mRNA) was reverse-transcribed into complementary DNA (cDNA) and subjected to polymerase chain reaction for the following cytokines: tumor necrosis factor-(alpha) (TNF-(alpha) ), interleukin-1(alpha) /(Beta) (IL- 1(alpha) /(Beta) ), interleukin-6 (IL-6), transforming growth factor-(Beta) 1 (TGF- (Beta) 1), macrophage colony stimulating factor (M-CSF), inducible nitric oxide synthase (iNOS), and glyceraldehyde 3-phosphate dehydrogenase (G3PDH). Histologically, lesions were confined to the photoreceptors, retinal pigment epithelium, and choroid. In laser-injured retinas, mRNA levels were elevated for IL-1(alpha) , TGF-(Beta) 1, iNOS, and G3PDH, but not TNF-(alpha) , IL-1(Beta) , or IL-6. It appears that the retina, in response to laser injury, upregulates a select number of cytokines in a time-course dependent fashion.

Aprataxin resolves adenylated RNA–DNA junctions to maintain genome integrity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tumbale, Percy; Williams, Jessica S.; Schellenberg, Matthew J.

2013-12-22

Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions. Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing amore » ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA–DNA, and acting in an RNA–DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure–function studies of human APTX–RNA–DNA–AMP–Zn complexes define a mechanism for detecting and reversing adenylation at RNA–DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA–DNA may contribute to neurological disease.« less

Soluble serum interleukin 2 receptor levels in leprosy patients

PubMed Central

Tung, K. S. K.; Umland, Edith; Matzner, P.; Nelson, K.; Schauf, Victoria; Rubin, L.; Wagner, D.; Scollard, D.; Vithayasai, Prakong; Vithayasai, Vicharn; Worobec, Sophie; Smith, T.; Suriyanond, Vinai

1987-01-01

Soluble interleukin 2 receptors (IL-2R) in sera of leprosy patients from Chiang Mai, Thailand, were quantified with a solid phase enzyme immunoassay using two monoclonal antibodies to the IL-2R. The IL-2R levels of untreated lepromatous, borderline lepromatous or midborderline patients and treated lepromatous and borderline lepromatous or treated borderline tuberculoid and tuberculoid patients were comparable to those of the Thai household or nonhousehold contacts; and they were significantly higher than the levels of USA control subjects. In contrast, IL-2R of untreated tuberculoid or borderline tuberculoid patients were significantly reduced. Patients with ongoing reversal reaction had very high circulating IL-2R, the levels of which correlated with fever and extent of skin lesions. Although erythrema nodosum leprosum patients also had elevated IL-2R levels, they were significantly below those of patients with reversal reaction. When treated with corticosteroid, precipitous reduction of IL-2R was noted in all patients with reversal reaction but not in patients with erythema nodosum leprosum. PMID:3115652

Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

PubMed

Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

2010-07-21

The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus.

PubMed

Jakovljevic, A; Andric, M; Nikolic, N; Coric, V; Krezovic, S; Carkic, J; Knezevic, A; Beljic-Ivanovic, K; Pljesa-Ercegovac, M; Miletic, M; Soldatovic, I; Radosavljevic, T; Jovanovic, T; Simic, T; Ivanovic, V; Milasin, J

2018-06-01

To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Reverse Dynamization

PubMed Central

Glatt, Vaida; Bartnikowski, Nicole; Quirk, Nicholas; Schuetz, Michael; Evans, Christopher

2016-01-01

Background: Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions. Methods: Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing. Results: In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification. Conclusions: These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully. Clinical Relevance: Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation. PMID:27098327

[The relationships among raphe magnus nucleus, locus coeruleus and dorsal motor nucleus of vagus in the descending regulation of gastric motility].

PubMed

Qiao, Hui; An, Shu-Cheng; Xu, Chang

2011-02-01

To explore the interrelationship among dorsal motor nucleus of the vagus (DMV), locus coeruleus (LC) and raphe magnus nucleus (NRM) in the mechanism of the descending regulation on gastric motility, which may constitute a parasympathetic local circuit, work as a neural center of gastric modulation in brainstem. Using nucleus location, electric stimulation and lesion, together with microinjection, and recording the inter-gastric pressure. (1) LC stimulation could inhibit the gastric motility significantly (P < 0.01), DMV lesion weaken this effect, while blocking the a receptor on DMV could reverse the effect. (2) NRM stimulation reduced the amplitude of gastric constriction (P < 0.01), DMV lesion could abolish the effect, but blocking the 5-HT2A receptor on DMV depressed the gastric motility heavily (P < 0.01) like NRM stimulation. While LC lesion could abolish the effect of NRM stimulation, and microinjection of ritanserin into LC could likewise abolish it. (1) LC inhibit the gastric motility via a receptor in DMV, and meanwhile may excite it through 5-HT2A receptor in DMV, these two ways work together to keeping the gastric motility amplitude normally. (2) NRM inhibit the gastric motility via 5-HT2A receptor in LC.

Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions.

PubMed

Arnt, J

1985-08-26

The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

New experimental results in atlas-based brain morphometry

NASA Astrophysics Data System (ADS)

Gee, James C.; Fabella, Brian A.; Fernandes, Siddharth E.; Turetsky, Bruce I.; Gur, Ruben C.; Gur, Raquel E.

1999-05-01

In a previous meeting, we described a computational approach to MRI morphometry, in which a spatial warp mapping a reference or atlas image into anatomic alignment with the subject is first inferred. Shape differences with respect to the atlas are then studied by calculating the pointwise Jacobian determinant for the warp, which provides a measure of the change in differential volume about a point in the reference as it transforms to its corresponding position in the subject. In this paper, the method is used to analyze sex differences in the shape and size of the corpus callosum in an ongoing study of a large population of normal controls. The preliminary results of the current analysis support findings in the literature that have observed the splenium to be larger in females than in males.

Motor Cortex Stimulation Reverses Maladaptive Plasticity Following Spinal Cord Injury

DTIC Science & Technology

2011-09-01

Additional anesthesia (10 mg/kg intraperitoneal, diluted ketamine 1:10 in saline) was administered whenneeded. Local anesthetic (2% lidocaine)was applied to...cord lesion. Under aseptic conditions, and using ketamine/xylazine anesthesia Figure 5. A representative example of a PO neuron in response to the... localized (Task 1b). • We found that the majority of ZI units enhanced by MCS receive direct inputs from the motor cortex (Task 1b). • We

Non-surgical management methods of noncavitated carious lesions.

PubMed

Tellez, Marisol; Gomez, Juliana; Kaur, Sundeep; Pretty, Iain A; Ellwood, Roger; Ismail, Amid I

2013-02-01

To critically appraise all evidence related to the efficacy of nonsurgical caries preventive methods to arrest or reverse the progression of noncavitated carious lesions (NCCls). A detailed search of Medline (via OVID), Cochrane Collaboration, Scielo, and EMBASE identified 625 publications. After title and abstract review, 103 publications were selected for further review, and 29 were finally included. The final publications evaluated the following therapies: fluorides (F) in varying vehicles (toothpaste, gel, varnish, mouthrinse, and combination), chlorhexidine (CHX) alone or in combination with F, resin infiltration (I), sealants (S), xylitol (X) in varying vehicles (lozenges, gum, or in combination with F and/or xylitol), casein phosphopeptide amorphous calcium phosphate (CPP-ACP) or in combination with calcium fluoride phosphate. All included studies were randomized clinical trials, were conducted with human subjects and natural NCCls, and reported findings that can yield outcomes measures such as caries incidence/increments, percentage of progression and/or arrest, odds ratio progression test to control, fluorescence loss/mean values, changes in lesion area/volume and lesion depth. Data were extracted from the selected studies and checked for errors. The quality of the studies was evaluated by three different methods (ADA, Cochrane, author's consensus). Sample size for these trials ranged between 15 and 3903 subjects, with a duration between 2 weeks and 4.02 years. More than half of the trials assessed had moderate to high risk of bias or may be categorized as 'poor'. The great majority (65.5%) did not use intention to treat analysis, 21% did not use any blinding techniques, and 41% reported concealment allocation procedures. Slightly more than half of the trials (55%) factored in background exposure to other fluoride sources, and only 41% properly adjusted for potential confounders. Fluoride interventions (varnishes, gels, and toothpaste) seem to have the most consistent benefit in decreasing the progression and incidence of NCCls. Studies using xylitol, CHX, and CPP-ACP vehicles alone or in combination with fluoride therapy are very limited in number and in the majority of the cases did not show a statistically significant reduction. Sealants and resin infiltration studies point to a potential consistent benefit in slowing the progression or reversing NCCls.

Arthroscopic management of posterior instability: evolution of technique and results.

PubMed

Savoie, Felix H; Holt, M Shaun; Field, Larry D; Ramsey, J Randall

2008-04-01

The purpose of this study was to evaluate the effectiveness of arthroscopic posterior shoulder reconstruction. We treated 136 shoulders in 131 patients with a diagnosis of primary posterior instability who failed 6 months of vigorous rehabilitation by operative stabilization between 1989 and 2001. Inclusion criterion was primary posterior instability that failed an extensive rehabilitative program with functional impairment and pain. Exclusion criterion was less than 12 months of follow-up and Suretac (Smith & Nephew, Andover, MA) or laser stabilization, leaving 92 shoulders in 90 patients available for the study (69 male, 21 female). Follow-up ranged from 12 to 132 months (average, 28 months). Each patient underwent diagnostic arthroscopy and surgical repair at the same time using one of several primary procedures. The procedure used was based on the pathologic entity noted at the time of surgery. At an average follow-up of 28 months, 97% of the shoulders were stable and considered a success based on the Neer-Foster rating scale. Posterior pathology varied, and a reverse Bankart lesion alone was found 51% of the time, a stretched posterior capsule 67% of the time, and a combination of a reverse Bankart lesion and capsular stretching 16% of the time. The rotator interval was obviously damaged in 61% of cases. Multiple accompanying lesions were found, including anterior-superior labral tears and SLAP tears (20%), superior glenohumeral ligament injury (7%), middle glenohumeral ligament injury (38%), anteroinferior glenohumaral ligament injury (37%), and an enlarged axillary pouch (20%). No essential lesion is present for posterior instability. Multiple varied pathologies will be present in a shoulder presenting with posterior instability. Arthroscopic surgery allows inspection of the joint and anatomic-specific repairs based on pathology. Careful attention to all the supporting structures of the shoulder, including the rotator interval, the anterior-superior labrum, and its attached superior glenohumeral ligament, the coracohumeral ligament, the inferior glenohumeral ligament complex, and the infraspinatus, in addition to the posterior labrum and capsule, allows excellent outcomes to be achieved with arthroscopic posterior reconstruction techniques. Level IV, therapeutic case series.

Involvement of interleukin-23 induced by Porphyromonas endodontalis lipopolysaccharide in osteoclastogenesis

PubMed Central

Ma, Nan; Yang, Di; Okamura, Hirohiko; Teramachi, Jumpei; Hasegawa, Tomokazu; Qiu, Lihong; Haneji, Tatsuji

2017-01-01

Periapical lesions are characterized by the destruction of periapical bone, and occur as a result of local inflammatory responses to root canal infection by microorganisms including Porphyromonas endodontalis (P. endodontalis). P. endodontalis and its primary virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical lesions and alveolar bone loss. Interleukin-23 (IL-23) is critical in the initiation and progression of periodontal disease via effects on peripheral bone metabolism. The present study investigated the expression of IL-23 in tissue where a periapical lesion was present, and the effect of P. endodontalis LPS on the expression of IL-23 in periodontal ligament (PDL) cells. Reverse transcription- quantitative polymerase chain reaction and immunohistochemistry revealed increased levels of IL-23 expression in tissue with periapical lesions compared with healthy PDL tissue. Treatment with P. endodontalis LPS increased the expression of IL-23 in the SH-9 human PDL cell line. BAY11-7082, a nuclear factor κB inhibitor, suppressed P. endodontalis LPS-induced IL-23 expression in SH-9 cells. Treatment of RAW264.7 cells with conditioned medium from P. endodontalis LPS-treated SH-9 cells promoted osteoclastogenesis. By contrast, RAW264.7 cells treated with conditioned medium from IL-23-knockdown SH-9 cells underwent reduced levels of osteoclastogenesis. The results of the present study indicated that the expression of IL-23 in PDL cells induced by P. endodontalis LPS treatment may be involved in the progression of periapical lesions via stimulation of the osteoclastogenesis process. PMID:28000855

Effects of Laser Physical Parameters on Lesion Size in Retinal Photocoagulation Surgery: Clinical OCT and Experimental Study

PubMed Central

Soleimani, A.; Rasta, S.H.; Banaei, T.; Asgharsharghi Bonab, A.

2017-01-01

Introduction: The aim of the present study was to determine burn intensity in retinal laser photocoagulation based on laser parameters; wavelength, power, beam size and pulse duration, using Optical Coherence Tomography (OCT), fundus camera, physical eye model and computer simulation in a clinical study. Materials and Methods: Participants were 10 adult patients between 50-80 years with proliferative diabetic retinopathy. A multicolor-photo coagulator with 532 nm green and 672 nm red for retina photocoagulation in diabetic retinopathy was used to investigate the participants. Lesion size was measured for spot sizes 50 and 100 μm, with 100 and 150 mW laser power, and pulse duration 50 and 100 ms by OCT. Artificial eye and Zemax-optical design software were used with the same laser parameters. Results: Appearance of OCT and fundus images showed direct relationship between retina burn size and lesion intensity with exposure time and power and also reverse relationship with laser spot size. Compared to red wavelength, burn size and lesion intensity increased in green wavelength. On the other hand, results from physical eye model were the same as clinical examination shown. Laser spot size in retina with Zemax simulation demonstrated that red wavelength was greater than green one. Conclusion: This study showed shorter pulses provide decrease in duration of laser surgery with significantly reduced pain. Results and calculations described in this article can help clinicians adjusting the required total coagulated area, the number of lesions and pattern density. PMID:29445713

Effects of Laser Physical Parameters on Lesion Size in Retinal Photocoagulation Surgery: Clinical OCT and Experimental Study.

PubMed

Soleimani, A; Rasta, S H; Banaei, T; Asgharsharghi Bonab, A

2017-12-01

The aim of the present study was to determine burn intensity in retinal laser photocoagulation based on laser parameters; wavelength, power, beam size and pulse duration, using Optical Coherence Tomography (OCT), fundus camera, physical eye model and computer simulation in a clinical study. Participants were 10 adult patients between 50-80 years with proliferative diabetic retinopathy. A multicolor-photo coagulator with 532 nm green and 672 nm red for retina photocoagulation in diabetic retinopathy was used to investigate the participants. Lesion size was measured for spot sizes 50 and 100 μm, with 100 and 150 mW laser power, and pulse duration 50 and 100 ms by OCT. Artificial eye and Zemax-optical design software were used with the same laser parameters. Appearance of OCT and fundus images showed direct relationship between retina burn size and lesion intensity with exposure time and power and also reverse relationship with laser spot size. Compared to red wavelength, burn size and lesion intensity increased in green wavelength. On the other hand, results from physical eye model were the same as clinical examination shown. Laser spot size in retina with Zemax simulation demonstrated that red wavelength was greater than green one. This study showed shorter pulses provide decrease in duration of laser surgery with significantly reduced pain. Results and calculations described in this article can help clinicians adjusting the required total coagulated area, the number of lesions and pattern density.

Highly differentiated keratinizing squamous cell cancer of the cervix: a rare, locally aggressive tumor not associated with human papillomavirus or squamous intraepithelial lesions.

PubMed

Morrison, C; Catania, F; Wakely, P; Nuovo, G J

2001-10-01

The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening.

Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

PubMed

Aridon, Paolo; Ragonese, Paolo; Di Benedetto, Norma; Grasso, Giovanni; Conaldi, Pier Giulio; D'Amelio, Marco; Savettieri, Giovanni

2009-12-01

Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma

PubMed Central

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W.; Novane, Nora; Shah, Jatin J.; Davis, Richard E.; Hou, Jian; Gagel, Robert F.; Yang, Jing

2016-01-01

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP upregulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP upregulated the methylation of IRF8, thereby enhanced expression of NFATc1, leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2DDR. Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K/Akt signaling, and increased DNMT3A expression, resulting in hypermethylation of RUNX2, osterix, and IRF8. This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. As TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. PMID:27559096

Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

PubMed

Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

2003-01-01

We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

Bone marrow lesions and subchondral bone pathology of the knee.

PubMed

Kon, Elizaveta; Ronga, Mario; Filardo, Giuseppe; Farr, Jack; Madry, Henning; Milano, Giuseppe; Andriolo, Luca; Shabshin, Nogah

2016-06-01

Bone marrow lesions (BMLs) around the knee are a common magnetic resonance imaging (MRI) finding. However, despite the growing interest on BMLs in multiple pathological conditions, they remain controversial not only for the still unknown role in the etiopathological processes, but also in terms of clinical impact and treatment. The differential diagnosis includes a wide range of conditions: traumatic contusion and fractures, cyst formation and erosions, hematopoietic and infiltrated marrow, developmental chondroses, disuse and overuse, transient bone marrow oedema syndrome and, lastly, subchondral insufficiency fractures and true osteonecrosis. Regardless the heterogeneous spectrum of these pathologies, a key factor for patient management is the distinction between reversible and irreversible conditions. To this regard, MRI plays a major role, leading to the correct diagnosis based on recognizable typical patterns that have to be considered together with coexistent abnormalities, age, and clinical history. Several treatment options have been proposed, from conservative to surgical approaches. In this manuscript the main lesion patterns and their management have been analysed to provide the most updated evidence for the differential diagnosis and the most effective treatment.

Rapid reversal of colonic pneumatosis with restoration of mesenteric arterial supply.

PubMed

Abidali, Hussein; Cole, Lauren; Seetharam, Anil Bellur

2018-06-07

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cystic lesions within the wall of the large intestine and presents along a spectrum of clinical severity ranging from benign to life threatening. Etiopathogenesis is multifactorial and postulated to result from either mechanical or bacterial causes. In this report, we present a patient with chronic abdominal pain evaluated with colonoscopy revealing segmental PCI isolated to the distal colon. Further investigation revealed an abdominal aortic aneurysm (AAA) compromising the inferior mesenteric artery takeoff. Endovascular repair of the AAA resulted in clinical resolution of abdominal pain and endoscopic resolution of PCI. To our knowledge, this is the first report to document endoscopic resolution of PCI with restoration of mesenteric arterial supply, highlighting vascular insufficiency as a predisposing and reversible pathogenic mechanism.

Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

PubMed

Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

2017-12-01

Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.

Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene: report of 2 infantile cases and review of the differential diagnosis of infantile pulmonary lesions.

PubMed

Tanaka, Mio; Kohashi, Kenichi; Kushitani, Kei; Yoshida, Misa; Kurihara, Sho; Kawashima, Masumi; Ueda, Yuka; Souzaki, Ryota; Kinoshita, Yoshiaki; Oda, Yoshinao; Takeshima, Yukio; Hiyama, Eiso; Taguchi, Tomoaki; Tanaka, Yukichi

2017-08-01

We report 2 infantile cases of pulmonary tumor carrying a chimeric A2M-ALK gene. A2M-ALK is a newly identified anaplastic lymphoma kinase (ALK)-related chimeric gene from a tumor diagnosed as fetal lung interstitial tumor (FLIT). FLIT is a recently recognized infantile pulmonary lesion defined as a mass-like lesion that morphologically resembles the fetal lung. Grossly, FLIT characteristically appears as a well-circumscribed spongy mass, whereas the tumors in these patients were solid and firm. Histologically, the tumors showed intrapulmonary lesions composed of densely proliferating polygonal or spindle-shaped mesenchymal cells with diffuse and dense infiltrations of inflammatory cells forming microcystic or micropapillary structures lined by thyroid transcription factor 1-positive pneumocytes, favoring inflammatory myofibroblastic tumor rather than FLIT. The proliferating cells were immunoreactive for ALK, and A2M-ALK was identified in both tumors with reverse-transcription polymerase chain reaction. The dense infiltration of inflammatory cells, immunoreactivity for ALK, and identification of an ALK-related chimeric gene suggested a diagnosis of inflammatory myofibroblastic tumor. Histologically, most reported FLITs show sparse inflammatory infiltrates and a relatively low density of interstitial cells in the septa, although prominent infiltration of inflammatory cells and high cellularity of interstitial cells are seen in some FLITs. The present cases suggest that ALK rearrangements, including the chimeric A2M-ALK gene, may be present in these infantile pulmonary lesions, especially those with inflammatory cell infiltration. We propose that these infantile pulmonary lesions containing a chimeric A2M-ALK gene be categorized as a specific type of inflammatory myofibroblastic tumor that develops exclusively in neonates and infants. Copyright © 2017 Elsevier Inc. All rights reserved.

Silver diagnosis in neuropathology: principles, practice and revised interpretation

PubMed Central

2007-01-01

Silver-staining methods are helpful for histological identification of pathological deposits. In spite of some ambiguities regarding their mechanism and interpretation, they are widely used for histopathological diagnosis. In this review, four major silver-staining methods, modified Bielschowsky, Bodian, Gallyas (GAL) and Campbell–Switzer (CS) methods, are outlined with respect to their principles, basic protocols and interpretations, thereby providing neuropathologists, technicians and neuroscientists with a common basis for comparing findings and identifying the issues that still need to be clarified. Some consider “argyrophilia” to be a homogeneous phenomenon irrespective of the lesion and the method. Thus, they seek to explain the differences among the methods by pointing to their different sensitivities in detecting lesions (quantitative difference). Comparative studies, however, have demonstrated that argyrophilia is heterogeneous and dependent not only on the method but also on the lesion (qualitative difference). Each staining method has its own lesion-dependent specificity and, within this specificity, its own sensitivity. This “method- and lesion-dependent” nature of argyrophilia enables operational sorting of disease-specific lesions based on their silver-staining profiles, which may potentially represent some disease-specific aspects. Furthermore, comparisons between immunohistochemical and biochemical data have revealed an empirical correlation between GAL+/CS-deposits and 4-repeat (4R) tau (corticobasal degeneration, progressive supranuclear palsy and argyrophilic grains) and its complementary reversal between GAL-/CS+deposits and 3-repeat (3R) tau (Pick bodies). Deposits containing both 3R and 4R tau (neurofibrillary tangles of Alzheimer type) are GAL+/CS+. Although no molecular explanations, other than these empiric correlations, are currently available, these distinctive features, especially when combined with immunohistochemistry, are useful because silver-staining methods and immunoreactions are complementary to each other. PMID:17401570

Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumaz, N.; Drougard, C.; Sarasin, A.

1993-11-15

The UV component of sunlight is the major carcinogen involved in the etiology of skin cancers. The authors have studied the rare, hereditary syndrome xeroderma pigmentosum (XP), which is characterized by a very high incidence of cutaneous tumors on exposed skin at an early age, probably due to a deficiency in excision repair of UV-induced lesions. It is interesting to determine the UV mutation spectrum in XP skin tumors in order to correlate the absence of repair of specific DNA lesions and the initiation of skin tumors. The p53 gene is frequently mutated in human cancers and represents a goodmore » target for studying mutation spectra since there are >100 potential sites for phenotypic mutations. Using reverse transcription-PCR and single-strand conformation polymorphism to analyze >40 XP skin tumors (mainly basal and squamous cell carcinomas), the authors have found that 40% (17 out of 43) contained at least one point mutation on the p53 gene. All the mutations were located at dipyrimidine sites, essentially at CC sequences, which are hot spots for UV-induced DNA lesions. Sixty-one percent of these mutations were tandem CC [yields] TT mutations considered to be unique to UV-induced lesions; these mutations are not observed in internal human tumors. All the mutations, except two, must be due to translesion synthesis of unrepaired dipyrimidine lesions left on the nontranscribed strand. These results show the existence of preferential repair of UV lesions [either pyrimidine dimers or pyrimidine-pyrimidone (6-4) photoproducts] on the transcribed strand in human tissues.« less

Estimation of the Mean Axon Diameter and Intra-axonal Space Volume Fraction of the Human Corpus Callosum: Diffusion q-space Imaging with Low q-values.

PubMed

Suzuki, Yuriko; Hori, Masaaki; Kamiya, Kouhei; Fukunaga, Issei; Aoki, Shigeki; VAN Cauteren, Marc

2016-01-01

Q-space imaging (QSI) is a diffusion-weighted imaging (DWI) technique that enables investigation of tissue microstructure. However, for sufficient displacement resolution to measure the microstructure, QSI requires high q-values that are usually difficult to achieve with a clinical scanner. The recently introduced "low q-value method" fits the echo attenuation to only low q-values to extract the root mean square displacement. We investigated the clinical feasibility of the low q-value method for estimating the microstructure of the human corpus callosum using a 3.0-tesla clinical scanner within a clinically feasible scan time. We performed a simulation to explore the acceptable range of maximum q-values for the low q-value method. We simulated echo attenuations caused by restricted diffusion in the intra-axonal space (IAS) and hindered diffusion in the extra-axonal space (EAS) assuming 100,000 cylinders with various diameters, and we estimated mean axon diameter, IAS volume fraction, and EAS diffusivity by fitting echo attenuations with different maximum q-values. Furthermore, we scanned the corpus callosum of 7 healthy volunteers and estimated the mean axon diameter and IAS volume fraction. Good agreement between estimated and defined values in the simulation study with maximum q-values of 700 and 800 cm(-1) suggested that the maximum q-value used in the in vivo experiment, 737 cm(-1), was reasonable. In the in vivo experiment, the mean axon diameter was larger in the body of the corpus callosum and smaller in the genu and splenium, and this anterior-to-posterior trend is consistent with previously reported histology, although our mean axon diameter seems larger in size. On the other hand, we found an opposite anterior-to-posterior trend, with high IAS volume fraction in the genu and splenium and a lower fraction in the body, which is similar to the fiber density reported in the histology study. The low q-value method may provide insights into tissue microstructure using a 3T clinical scanner within clinically feasible scan time.

Leprosy reactions in postelimination stage: the Bangladesh experience.

PubMed

Mowla, M R; Ara, S; Mizanur Rahman, A F M; Tripura, S P; Paul, S

2017-04-01

Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. To describe the pattern and prevalence of leprosy reactions in the postelimination stage. A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services. © 2016 European Academy of Dermatology and Venereology.

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

PubMed

Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

2017-04-01

Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gallium scanning in cerebral and cranial infections. [/sup 67/Ga, /sup 99m/Tc tracer techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waxman, A.D.; Siemsen, J.K.

1976-08-01

Eighteen patients with cranial or intracranial infections were studied with technetium and gallium brain scans. Seven of 18 lesions were noted with gallium and not with pertechnetate, while the reverse pattern was not seen. Brain abscesses were visualized with gallium but not with pertechnetate in two of five cases. Osteomyelitis of the skull and mastoiditis showed intense gallium uptake in all cases, while meningitis or cerebritis gave inconsistent results.

Thirteen Week Oral Toxicity Study of WR238605 with a Thirteen Week Recovery Period in Dogs. Volume 1

DTIC Science & Technology

1993-06-11

SOURCE OF FUNDING NUMBERS PROGRAM ELEMENT NO. 63807A PROJECT NO. 30463807 TASK NO. QC WORK UNIT ACCESSION NO. 073 11. TITLE (Include...reversible, except for the lung lesions (subacute inflammation) and the microscopic changes secondary to the observed hemolytic anemia ( hepatic ... hepatic hemosiderosis). Based upon the these findings, the no observed effect level (NOEL) in this study was equivocal, but was considered to be near the

Population Based Assessment of MHC Class 1 Antigens Down Regulation as Marker in Increased Risk for Development and Progression of Breast Cancer From Benign Breast Lesions

DTIC Science & Technology

2006-01-01

isolated using a routine salting-out method (DNA E-Z Prepkit, Orchid Diagnostics Europe, St Katelijne Waver, Belgium). Sequence based typing In...electrophoresis using ethidiumbromide to show the single 2 KB band before sequencing. Next, sequencing reactions were performed separately for exons 2, 3...Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNulty, W.P.

In rhesus macaques (Macaca mulatta), consumption of food containing commercial polychlorinated biphenyl (PCB) mixtures, some pure polychlorobiphenyl congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) caused the same clinical toxic manifestations and histopathologic lesions, although the potencies of the toxicants covered a range of five orders of magnitude. Recovery from poisoning by 3,4,3',4'-tetrachlorobiphenyl (34TCB) or TCDF was rapid, whereas recovery from poisoning by Aroclor 1242, 3,4,5,3',4',5'-hexachlorobiphenyl (345HCB), or TCDD was protracted, if it occurred at all. 34TCB did not appreciably accumulate in body fat, but the level of 345HCB in fat rose steadily during ingestion. Among the symmetrical tetra- and hexachlorobiphenyl isomersmore » tested, subacute oral toxicity could be demonstrated only for those without ortho chlorine substitutions. The principal demonstrable histopathological lesions, bone marrow excepted, were metaplasias in some specialized epithelial structures, such as sebaceous glands, nail beds, gastric mucosa, ameloblast, and thymic corpuscles. These changes were interpreted as toxicant-induced, reversible redirection of differentiation. this aberration was wholly reversible. TCDD and 34TCB caused abortions when given in one or a few oral doses early in pregnancy. At the total doses used (1 or 5 g/kg of body weight for TCDD, 3 or 0.6 mg/kg of body weight for 34TCB), maternal toxicity was frequently apparent subsequent to the abortion.« less

Dermal fibroblasts from acute inflamed atopic dermatitis lesions display increased eotaxin/CCL11 responsiveness to interleukin-4 stimulation.

PubMed

Gahr, N; Fölster-Holst, R; Weichenthal, M; Christophers, E; Schröder, J-M; Bartels, J

2011-03-01

The presence of eosinophils and/or eosinophil-derived products in the dermis is characteristic for involved skin of patients with atopic dermatitis and contributes to the observed tissue injury. CCL11 is a potent chemoattractant and activator of human eosinophils and interleukin (IL)-4 is a potent inducer of CCL11 expression in dermal fibroblasts. As increased fibroblast CCL11 expression may explain eosinophilic infiltration of involved skin areas in atopic dermatitis, we asked whether dermal fibroblasts from atopic patients differ from fibroblasts of healthy individuals in their ability to express CCL11. We compared IL-4-induced CCL11 mRNA expression using reverse transcription-polymerase chain reaction from cultured dermal fibroblasts derived from biopsies of chronic lesional and acute lesional atopic skin as well as from skin biopsies derived from normal skin of healthy donors. Considerable variability in IL-4-induced relative CCL11 mRNA expression was detected in fibroblasts derived from biopsies of different individuals. The lowest median IL-4 concentration inducing half maximal CCL11 mRNA expression (EC(50)) was found in fibroblasts derived from acute inflamed atopic lesions. Inducibility of CCL11 in dermal fibroblasts upon stimulation with Th2 cytokines explains the tissue eosinophilia observed in the presence of Th2 cytokines and the localization of eosinophils to the dermis. Decreased EC(50) values of IL-4-induced CCL11 expression in fibroblasts from acute inflamed atopic skin lesions indicates increased IL-4 responsiveness in these lesions and further substantiates the special role for IL-4-induced dermal fibroblast CCL11 expression in acute lesions. Variable CCL11 expression in fibroblasts from different patients with atopic dermatitis indicates heterogeneity of factors determining atopic phenotype in atopic dermatitis. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is neuroprotective in newborn mice.

PubMed

Medja, Fadia; Lelièvre, Vincent; Fontaine, Romain H; Lebas, Fanny; Leroux, Philippe; Ouimet, Tanja; Saria, Alois; Rougeot, Catherine; Dournaud, Pascal; Gressens, Pierre

2006-12-01

Excitotoxic damage appears to be a critical factor in the formation of perinatal brain lesions associated with cerebral palsy (CP). When injected into newborn mice, the glutamatergic analogue, ibotenate, produces cortical lesions and white matter cysts that mimic human perinatal brain lesions. Neuropeptides are neuronal activity modulators and could therefore modulate glutamate-induced lesions. However, neuropeptides are rapidly degraded by peptidases. Racecadotril, which is rapidly metabolized to its active metabolite thiorphan, is a neutral endopeptidase (NEP) inhibitor used in clinical practice for diarrhoea with a remarkable safety profile. This study aimed to test the original hypothesis that thiorphan could be neuroprotective against ibotenate-induced lesions in newborn mice. Intraperitoneal administration of thiorphan reduced ibotenate-induced cortical lesions by up to 57% and cortical caspase-3 cleavage by up to 59%. This neuroprotective effect was long-lasting and was still observed when thiorphan was administered 12 h after the insult, showing a remarkable window for therapeutic intervention. Further supporting the neuroprotective effect of pharmacological blockade of NEP, mouse pups with a genetic deletion of NEP displayed a significantly reduced size of the ibotenate-induced cortical grey matter lesion when compared with wild-type animals. Thiorphan effects were mimicked by substance P (SP) and, in a less potent manner, by neurokinin A. Thiorphan effects were inhibited by blockers of NK1 and NK2 receptors. Real-time reverse transcription-polymerase chain reaction, autoradiography and immunohistochemistry confirmed the expression of NK1 and NK2 receptors in the neonatal murine neocortex. These data demonstrate that thiorphan prevents neonatal excitotoxic cortical damage, an effect largely mediated by SP. Thiorphan could represent a promising drug for the prevention of CP, which remains a challenging disease. In a broader context, these results also raise potential implications for the prevention of neurodegenerative diseases involving glutamate-mediated excitotoxic neuronal death.

Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.

PubMed

Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N

2001-01-01

Liver lesions and portal hypertension in rats, following chronic alcohol administration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg b.w. of alcohol given in drinking water for 3 months, were counteracted by a stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in a variety of models of gastrointestinal or liver lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughout either the whole 3 months period (1) or the last month only (2) (last application 24 h before sacrifice). In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all control saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats that received gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats. Besides, a raised surface area (microm(2)) and increased circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver), an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were markedly attenuated (values less than in drinking controls, still higher than in healthy rats, i.e. circumference and area of hepatocytes nucleus). On the other hand, ranitidine application attenuated only steatosis development. In summary, despite continuous chronic alcohol drinking, pentadecapeptide BPC 157, and propranolol may prevent portal hypertension as well as reverse already established portal hypertension along with related liver disturbances.

Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States

PubMed Central

Kallischnigg, Gerd; Weitkunat, Rolf; Lee, Peter N

2008-01-01

Background How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients), and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia) and from the USA. Methods Experimental and epidemiological studies published in 1963–2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain. Results Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting. Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases. Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco. Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries. Oral pain: Limited evidence precludes any clear conclusion. Conclusion This review confirms the strong association of current use of smokeless tobacco, particularly snuff, with prevalence of oral mucosal lesions. It provides suggestive evidence of an association of snuff use with gingival recession and attachment loss, and of chewing tobacco with dental caries. While smokeless tobacco clearly increases risk of oral mucosal lesions, interpretation for other endpoints is limited by study weaknesses, including poor confounding control. PMID:18452601

Age-Specific Dynamics of Corpus Callosum Development in Children and its Peculiarities in Infantile Cerebral Palsy.

PubMed

Krasnoshchekova, E I; Zykin, P A; Tkachenko, L A; Aleksandrov, T A; Sereda, V M; Yalfimov, A N

2016-10-01

The age dynamics of corpus callosum development was studied on magnetic resonance images of the brain in children aged 2-11 years without neurological abnormalities and with infantile cerebral palsy. The areas of the total corpus callosum and its segments are compared in the midsagittal images. Analysis is carried out with the use of an original formula: proportion of areas of the anterior (genu, CC2; and anterior part, CC3) and posterior (isthmus, CC6 and splenium, CC7) segments: kCC=(CC2+CC3)×CC6/CC7. The results characterize age-specific dynamics of the corpus callosum development and can be used for differentiation, with high confidence, of the brain of children without neurological abnormalities from the brain patients with infantile cerebral palsy.

Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy

PubMed Central

de Mattos Barbosa, Mayara Garcia; de Andrade Silva, Bruno Jorge; Assis, Tayná Quintella; da Silva Prata, Rhana Berto; Ferreira, Helen; Andrade, Priscila Ribeiro; da Paixão de Oliveira, Jéssica Araújo; Sperandio da Silva, Gilberto Marcelo; da Costa Nery, José Augusto; Sarno, Euzenir Nunes; Pinheiro, Roberta Olmo

2018-01-01

Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of multibacillary leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in multibacillary leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.

Treatment outcomes for professional voice users.

PubMed

Wingate, Judith M; Brown, William S; Shrivastav, Rahul; Davenport, Paul; Sapienza, Christine M

2007-07-01

Professional voice users comprise 25% to 35% of the U.S. working population. Their voice problems may interfere with job performance and impact costs for both employers and employees. The purpose of this study was to examine treatment outcomes of two specific rehabilitation programs for a group of professional voice users. Eighteen professional voice users participated in this study; half had complaints of throat pain or vocal fatigue (Dysphonia Group), and half were found to have benign vocal fold lesions (Lesion Group). One group received 5 weeks of expiratory muscle strength training followed by six sessions of traditional voice therapy. Treatment order was reversed for the second group. The study was designed as a repeated measures study with independent variables of treatment order, laryngeal diagnosis (lesion vs non-lesion), gender, and time. Dependent variables included maximum expiratory pressure (MEP), Voice Handicap Index (VHI) score, Vocal Rating Scale (VRS) score, Voice Effort Scale score, phonetogram measures, subglottal pressures, and acoustic and perceptual measures. Results showed significant improvements in MEP, VHI scores, and VRS scores, subglottal pressure for loud intensity, phonetogram area, and dynamic range. No significant difference was found between laryngeal diagnosis groups. A significant difference was not observed for treatment order. It was concluded that the combined treatment was responsible for the improvements observed. The results indicate that a combined modality treatment may be successful in the remediation of vocal problems for professional voice users.

Evaluation of the factors influencing brain language laterality in presurgical planning.

PubMed

Batouli, Seyed Amir Hossein; Hasani, Nafiseh; Gheisari, Sara; Behzad, Ebrahim; Oghabian, Mohammad Ali

2016-10-01

Brain lesions cause functional deficits, and one treatment for this condition is lesion resection. In most cases, presurgical planning (PSP) and the information from laterality indices are necessary for maximum preservation of the critical functions after surgery. Language laterality index (LI) is reliably estimated using functional magnetic resonance imaging (fMRI); however, this measure is under the influence of some external factors. In this study, we investigated the influence of a number of factors on language LI, using data from 120 patients (mean age=35.65 (±13.4) years) who underwent fMRI for PSP. Using two proposed language tasks from our previous works, brain left hemisphere was showed to be dominant for the language function, although a higher LI was obtained using the "Word Generation" task, compared to the "Reverse Word Reading". In addition, decline of LIs with age, and lower LI when the lesion invaded brain language area were observed. Meanwhile, gender, lesion side (affected hemisphere), LI calculation strategy, and fMRI analysis Z-values did not statistically show any influences on the LIs. Although fMRI is widely used to estimate language LI, it is shown here that in order to present a reliable language LI and to correctly select the dominant hemisphere of the brain, the influence of external factors should be carefully considered. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Does cone beam CT actually ameliorate stab wound analysis in bone?

PubMed

Gaudio, D; Di Giancamillo, M; Gibelli, D; Galassi, A; Cerutti, E; Cattaneo, C

2014-01-01

This study aims at verifying the potential of a recent radiological technology, cone beam CT (CBCT), for the reproduction of digital 3D models which may allow the user to verify the inner morphology of sharp force wounds within the bone tissue. Several sharp force wounds were produced by both single and double cutting edge weapons on cancellous and cortical bone, and then acquired by cone beam CT scan. The lesions were analysed by different software (a DICOM file viewer and reverse engineering software). Results verified the limited performances of such technology for lesions made on cortical bone, whereas on cancellous bone reliable models were obtained, and the precise morphology within the bone tissues was visible. On the basis of such results, a method for differential diagnosis between cutmarks by sharp tools with a single and two cutting edges can be proposed. On the other hand, the metrical computerised analysis of lesions highlights a clear increase of error range for measurements under 3 mm. Metric data taken by different operators shows a strong dispersion (% relative standard deviation). This pilot study shows that the use of CBCT technology can improve the investigation of morphological stab wounds on cancellous bone. Conversely metric analysis of the lesions as well as morphological analysis of wound dimension under 3 mm do not seem to be reliable.

Spared Anterograde Memory for Shock-Probe Fear Conditioning After Inactivation of the Amygdala

PubMed Central

Lehmann, Hugo; Treit, Dallas; Parent, Marise B.

2003-01-01

Previous studies have shown that amygdala lesions impair avoidance of an electrified probe. This finding has been interpreted as indicating that amygdala lesions reduce fear. It is unclear, however, whether amygdala-lesioned rats learn that the probe is associated with shock. If the lesions prevent the formation of this association, then pretraining reversible inactivation of the amygdala should impair both acquisition and retention performance. To test this hypothesis, the amygdala was inactivated (tetrodotoxin; TTX; 1 ng/side) before a shock-probe acquisition session, and retention was tested 4 d later. The data indicated that, compared with rats infused with vehicle, rats infused with TTX received more shocks during the acquisition session, but more importantly, were not impaired on the retention test. In Experiment 2, we assessed whether the spared memory on the retention test was caused by overtraining during acquisition. We used the same procedure as in Experiment 1, with the exception that the number of shocks the rats received during the acquisition session was limited to four. Again the data indicated that amygdala inactivation did not impair performance on the retention test. These results indicate that amygdala inactivation does not prevent the formation of an association between the shock and the probe and that shock-probe deficits during acquisition likely reflect the amygdala's involvement in other processes. PMID:12888544

Involvement of interleukin‑23 induced by Porphyromonas endodontalis lipopolysaccharide in osteoclastogenesis.

PubMed

Ma, Nan; Yang, Di; Okamura, Hirohiko; Teramachi, Jumpei; Hasegawa, Tomokazu; Qiu, Lihong; Haneji, Tatsuji

2017-02-01

Periapical lesions are characterized by the destruction of periapical bone, and occur as a result of local inflammatory responses to root canal infection by microorganisms including Porphyromonas endodontalis (P. endodontalis). P. endodontalis and its primary virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical lesions and alveolar bone loss. Interleukin‑23 (IL‑23) is critical in the initiation and progression of periodontal disease via effects on peripheral bone metabolism. The present study investigated the expression of IL‑23 in tissue where a periapical lesion was present, and the effect of P. endodontalis LPS on the expression of IL‑23 in periodontal ligament (PDL) cells. Reverse transcription‑ quantitative polymerase chain reaction and immunohistochemistry revealed increased levels of IL‑23 expression in tissue with periapical lesions compared with healthy PDL tissue. Treatment with P. endodontalis LPS increased the expression of IL‑23 in the SH‑9 human PDL cell line. BAY11‑7082, a nuclear factor κB inhibitor, suppressed P. endodontalis LPS‑induced IL‑23 expression in SH‑9 cells. Treatment of RAW264.7 cells with conditioned medium from P. endodontalis LPS‑treated SH‑9 cells promoted osteoclastogenesis. By contrast, RAW264.7 cells treated with conditioned medium from IL‑23‑knockdown SH‑9 cells underwent reduced levels of osteoclastogenesis. The results of the present study indicated that the expression of IL‑23 in PDL cells induced by P. endodontalis LPS treatment may be involved in the progression of periapical lesions via stimulation of the osteoclastogenesis process.

Nanosized zinc oxide particles do not promote DHPN-induced lung carcinogenesis but cause reversible epithelial hyperplasia of terminal bronchioles.

PubMed

Xu, Jiegou; Futakuchi, Mitsuru; Alexander, David B; Fukamachi, Katsumi; Numano, Takamasa; Suzui, Masumi; Shimizu, Hideo; Omori, Toyonori; Kanno, Jun; Hirose, Akihiko; Tsuda, Hiroyuki

2014-01-01

Zinc oxide (ZnO) is known to induce lung toxicity, including terminal bronchiolar epithelial hyperplasia, which gives rise to concerns that nanosized ZnO (nZnO) might lead to lung carcinogenesis. We studied the tumor promoting activity of nZnO by an initiation-promotion protocol using human c-Ha-ras proto-oncogene transgenic rats (Hras128 rats). The rats were given 0.2 % N-nitrosobis(2-hydroxypropyl)amine (DHPN) in the drinking water for 2 weeks and then treated with 0.5 ml of 250 or 500 μg/ml nZnO suspension by intra-pulmonary spraying once every 2 weeks for a total of 7 times. Treatment with nZnO particles did not promote DHPN-induced lung carcinogenesis. However, nZnO dose-dependently caused epithelial hyperplasia of terminal bronchioles (EHTB) and fibrosis-associated interstitial pneumonitis (FAIP) that were independent of DHPN treatment. Tracing the fate of EHTB lesions in wild-type rats indicated that the hyperplastic lesions almost completely disappeared within 12 weeks after the last nZnO treatment. Since nZnO particles were not found in the lung and ZnCl2 solution induced similar lung lesions and gene expression profiles, the observed lesions were most likely caused by dissolved Zn(2+). In summary, nZnO did not promote carcinogenesis in the lung and induced EHTB and FAIP lesions that regressed rapidly, probably due to clearance of surplus Zn(2+) from the lung.

Effect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleus

PubMed Central

Pezzato, Fernanda A.; Can, Adem; Hoshino, Katsumasa; Horta, José de Anchieta C.; Mijares, Miriam G.

2014-01-01

Rationale Alterations in brainstem circuits have been proposed as a possible mechanism underlying the etiology of mood disorders. Projections from the median raphe nucleus (MnR) modulate dopaminergic activity in the forebrain and are also part of a behavioral disinhibition/inhibition system that produces phenotypes resembling behavioral variations manifested during manic and depressive phases of bipolar disorder. Objective Assess the effect of chronic lithium treatment on behavioral disinhibition induced by MnR lesions. Methods MnR electrolytic lesions were performed in C57BL/6J mice, with sham operated and intact animals as control groups. Following recovery, mice were chronically treated with lithium (LiCl, added in chow) followed by behavioral testing. Results MnR lesion induced manic-like behavioral alterations including hyperactivity in the open field (OF), stereotyped circling, anxiolytic/risk taking in the elevated plus maze (EPM) and light/dark box (LDB) tests, and increased basal body temperature. Lithium was specifically effective in reducing OF hyperactivity and stereotypy but did not reverse (EPM) or had a nonspecific effect (LDB) on anxiety/risk taking measures. Additionally, lithium decreased saccharin preference and prevented weight loss during single housing. Conclusions Our data support electrolytic lesions of the MnR as an experimental model of a hyper-excitable/disinhibited phenotype consistent with some aspects of mania that are attenuated by the mood stabilizer lithium. Given lithium’s relatively specific efficacy in treating mania, these data support the hypothesis that manic symptoms derive not only from the stimulation of excitatory systems but also from inactivation or decreased activity of inhibitory mechanisms. PMID:25345734

Ovine and Bovine Congenital Abnormalities Associated With Intrauterine Infection With Schmallenberg Virus.

PubMed

Peperkamp, N H; Luttikholt, S J; Dijkman, R; Vos, J H; Junker, K; Greijdanus, S; Roumen, M P; van Garderen, E; Meertens, N; van Maanen, C; Lievaart, K; van Wuyckhuise, L; Wouda, W

2015-11-01

In December 2011, a previously unknown congenital syndrome of arthrogryposis and hydranencephaly in sheep and cattle appeared in the Netherlands as an emerging epizootic due to Schmallenberg virus (SBV). Gross lesions in 102 lambs and 204 calves included porencephaly, hydranencephaly, cerebellar dysplasia and dysplasia of the brainstem and spinal cord, a flattened skull with brachygnathia inferior, arthrogryposis, and vertebral column malformations. Microscopic lesions in the central nervous system showed rarefaction and cavitation in the white matter, as well as degeneration, necrosis, and loss of neurons in the gray matter. Brain and spinal cord lesions were more severe in lambs than in calves. Ovine and bovine cases examined early in the outbreak showed encephalomyelitis. SBV infection was confirmed by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in brain samples in 46 of 102 lambs (45%) and in 32 of 204 calves (16%). Immunohistochemistry, performed on tissue samples from 18 RT-qPCR-positive lambs, confirmed the presence of bunyaviral antigen in neurons of the brain in 16 cases. SBV antibodies were detected by enzyme-linked immunosorbent assay in fetal blood in 56 of 61 sampled ovine cases (92%). In a virus neutralization test, all tested dams of affected newborns, 46 ewes and 190 cows, were seropositive. Compared with other teratogenic viral infections, the pathogenesis and lesions of SBV in sheep and cattle fetuses are similar to those of other ruminant orthobunyaviruses. However, the loss of spinal ventral motor neurons and their tracts, resulting in micromyelia, distinguishes SBV infection from other viral central nervous system lesions in newborn ruminants. © The Author(s) 2014.

Ameliorative effects of Artemisia argyi Folium extract on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like lesions in BALB/c mice

PubMed Central

Han, Hyoung-Min; Kim, Seung-Ju; Kim, Jong-Sik; Kim, Bum Hoi; Lee, Hai Woong; Lee, Yong Tae; Kang, Kyung-Hwa

2016-01-01

Artemisia argyi Folium has been used to treat skin diseases, including eczema and dermatitis, in South Korean medicine. The present study investigated the curative effects of Artemisia argyi Folium extract (AAFE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in a BALB/c mouse model. Briefly, the dorsal skin of the BALB/c mice was sensitized three times with DNCB, whereas the ears were challenged twice. Repeated treatment with DNCB induced AD-like lesions. The effects of AAFE on AD-like lesions were evaluated by clinical observation, histopathological analysis, immunohistochemistry and enzyme-linked immunosorbent assay. In addition, reverse transcription-polymerase chain reaction and western blotting were performed. Treatment with AAFE reduced AD-like lesions, as determined by clinical observation, histopathological analysis, and detection of the serum levels of histamine, immunoglobulin E and cytokines. With regards to its mechanism of action, AAFE inhibited the phosphorylation of Lck/yes-related novel tyrosine kinase (Lyn), spleen tyrosine kinase (Syk), mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K)/Akt and IκBα, which have essential roles in the production of various cytokines in lymph nodes. The suppressive activity of AAFE may be due to the inhibition of a series of immunopathological events, including the release of proinflammatory cytokines. The results of the present study strongly suggest that AAFE exerts an anti-AD effect by inhibiting the Lyn, Syk, MAPKs, PI3K/Akt and IκBα pathways. Therefore, AAFE may be considered an effective herbal remedy for the treatment of AD. PMID:27571702

Impact of the Intracoronary Rendezvous technique on coronary angioplasty for chronic total occlusion.

PubMed

Nihei, Taro; Yamamoto, Yoshito; Kudo, Shun; Hanawa, Kenichiro; Hasebe, Yuhi; Takagi, Yusuke; Minatoya, Yutaka; Sugi, Masafumi; Shimokawa, Hiroaki

2017-10-01

The Rendezvous technique, which requires bidirectional wiring, is one of the useful methods for improving the success rate of recanalization for chronic total occlusion (CTO) in the field of peripheral intervention. Recently, advanced new devices for percutaneous coronary intervention have enabled us to perform the Rendezvous technique for peripheral as well as for coronary CTO lesions. We used the Intracoronary Rendezvous technique to perform angioplasty for coronary CTO. "Intracoronary Rendezvous" means that Rendezvous was achieved within the CTO lesion. From March 2009 to November 2015, 189 patients underwent CTO angioplasty at our institute, and we treated 10 patients with the Intracoronary Rendezvous technique. This technique involves crossing the Gaia series guidewire to the contralateral Corsair microcatheter located inside the plaque of CTO lesions. The majority of the CTO sites examined were in the proximal RCA (60 %). Lesion length of the occlusion was relatively long (64.4 ± 12.2 mm). Using the biplane imaging system, we were able to control the Gaia guidewires in a specific direction. Furthermore, if the antegrade and retrograde wires can be advanced into contiguous space inside the CTO lesion, we intentionally entered either wire into the contralateral Corsair microcatheter, followed by successful CTO crossing. CTO recanalization was completed for all patients without controlled antegrade retrograde subintimal tracking (CART) or reverse CART. No major complications occurred during hospitalization. These results indicate that the Rendezvous technique, assisted by new devices and a biplane imaging system, represents one of the primary options to achieve successful coronary CTO recanalization.

Processing of visual gravitational motion in the peri-sylvian cortex: Evidence from brain-damaged patients.

PubMed

Maffei, Vincenzo; Mazzarella, Elisabetta; Piras, Fabrizio; Spalletta, Gianfranco; Caltagirone, Carlo; Lacquaniti, Francesco; Daprati, Elena

2016-05-01

Rich behavioral evidence indicates that the brain estimates the visual direction and acceleration of gravity quite accurately, and the underlying mechanisms have begun to be unraveled. While the neuroanatomical substrates of gravity direction processing have been studied extensively in brain-damaged patients, to our knowledge no such study exists for the processing of visual gravitational motion. Here we asked 31 stroke patients to intercept a virtual ball moving along the vertical under either natural gravity or artificial reversed gravity. Twenty-seven of them also aligned a luminous bar to the vertical direction (subjective visual vertical, SVV). Using voxel-based lesion-symptom mapping as well as lesion subtraction analysis, we found that lesions mainly centered on the posterior insula are associated with greater deviations of SVV, consistent with several previous studies. Instead, lesions mainly centered on the parietal operculum decrease the ability to discriminate natural from unnatural gravitational acceleration with a timed motor response in the interception task. Both the posterior insula and the parietal operculum belong to the vestibular cortex, and presumably receive multisensory information about the gravity vector. We speculate that an internal model estimating the effects of gravity on visual objects is constructed by transforming the vestibular estimates of mechanical gravity, which are computed in the brainstem and cerebellum, into internalized estimates of virtual gravity, which are stored in the cortical vestibular network. The present lesion data suggest a specific role for the parietal operculum in detecting the mismatch between predictive signals from the internal model and the online visual signals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Features of electrocardiogram in patients with stenosis of the proximal right coronary artery

PubMed Central

Koh, Moo Seong; Lee, Jae Hoon; Jeong, Jin Woo; Chung, Jun Young

2017-01-01

Background/Aims Prediction of lesions of the proximal right coronary artery (pRCA) through electrocardiogram (ECG) is very important because pRCA occlusion has many complications and a high mortality rate, which has frequently been related with right ventricular infarction. The purpose of this study was to devise a screening tool that takes into account multiple leads from a 12-lead ECG to predict the pRCA lesion. Methods A hundred and fifty-eight patients who were diagnosed as acute coronary syndrome and had a pure lesion of RCA or left circumf lex artery (LCX) by ECGs and angiographic findings were enrolled retrospectively. Forty-eight patients with a pure pRCA occlusion were compared to a control group of 110 patients who were diagnosed as having either a pure mid to distal RCA lesion (57 patients) or a pure LCX lesion (53 patients). Results ECGs of patients in the pRCA group showed more prominent ST depression in lead I (p = 0.001) and ST elevation in V1 (p = 0.002) than in the control group. The combination of ST depression (≤ 0 mm) in I and ST elevation (> 0.5 mm) in V1 was the best diagnostic tool (area under the curve, 0.84). Conclusions ST changes in leads V1 and I allow more accurate prediction of pRCA occlusion than other criteria, such as the difference between ST elevation of leads II and III or vector direction and amplitude. These variables could help to screen for right ventricular infarction before performing reverse ECG and predicting prognosis. PMID:28190326

Features of electrocardiogram in patients with stenosis of the proximal right coronary artery.

PubMed

Koh, Moo Seong; Lee, Jae Hoon; Jeong, Jin Woo; Chung, Jun Young

2017-03-01

Prediction of lesions of the proximal right coronary artery (pRCA) through electrocardiogram (ECG) is very important because pRCA occlusion has many complications and a high mortality rate, which has frequently been related with right ventricular infarction. The purpose of this study was to devise a screening tool that takes into account multiple leads from a 12-lead ECG to predict the pRCA lesion. A hundred and fifty-eight patients who were diagnosed as acute coronary syndrome and had a pure lesion of RCA or left circumf lex artery (LCX) by ECGs and angiographic findings were enrolled retrospectively. Forty-eight patients with a pure pRCA occlusion were compared to a control group of 110 patients who were diagnosed as having either a pure mid to distal RCA lesion (57 patients) or a pure LCX lesion (53 patients). ECGs of patients in the pRCA group showed more prominent ST depression in lead I ( p = 0.001) and ST elevation in V1 ( p = 0.002) than in the control group. The combination of ST depression (≤ 0 mm) in I and ST elevation (> 0.5 mm) in V1 was the best diagnostic tool (area under the curve, 0.84). ST changes in leads V1 and I allow more accurate prediction of pRCA occlusion than other criteria, such as the difference between ST elevation of leads II and III or vector direction and amplitude. These variables could help to screen for right ventricular infarction before performing reverse ECG and predicting prognosis.

Response disengagement on a spatial self-ordered sequencing task: effects of regionally selective excitotoxic lesions and serotonin depletion within the prefrontal cortex.

PubMed

Walker, Susannah C; Robbins, Trevor W; Roberts, Angela C

2009-05-06

Prefrontal cortex (PFC) is critical for self-ordered response sequencing. Patients with frontal lobe damage are impaired on response sequencing tasks, and increased blood flow has been reported in ventrolateral and dorsolateral PFC in subjects performing such tasks. Previously, we have shown that large excitotoxic lesions of the lateral PFC (LPFC) and orbitofrontal cortex FC (OFC), but not global prefrontal dopamine depletion, markedly impaired marmoset performance on a spatial self-ordered sequencing task (SSOST). To determine whether LPFC or OFC was responsible for the previously observed impairments and whether the underlying neural mechanism was modulated by serotonin, the present study compared the effects of selective LPFC and OFC excitotoxic lesions and 5,7-DHT-induced PFC serotonin depletions in marmosets on SSOST performance. Severe and long-lasting impairments in SSOST performance, including robust perseverative responding, followed LPFC but not OFC lesions. The deficit was ameliorated by task manipulations that precluded perseveration. Depletions of serotonin within LPFC and OFC had no effect, despite impairing performance on a visual discrimination reversal task, thus providing further evidence for differential monaminergic regulation of prefrontal function. In the light of the proposed attentional control functions of ventrolateral PFC and the failure of LPFC-lesioned animals to disengage from the immediately preceding response, it is proposed that this deficit may be due to a failure to attend to and register that a response has been made and thus should not be repeated. However, 5-HT does not appear to be implicated in this response inhibitory capacity.

Reversible posterior leukoencephalopathy syndrome secondary to systemic-onset juvenile idiopathic arthritis: A case report and review of the literature.

PubMed

Zhang, Pingping; Li, Xiaofeng; Li, Yating; Wang, Jing; Zeng, Huasong; Zeng, Xiaofeng

2015-01-01

Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical syndrome based on changes in clinical imaging, and it has been reported to mainly occur in adults. However, it has been recently discovered that RPLS is also prevalent in infant patients, particularly in those using glucocorticoids, immunosuppressant medications and cytotoxic drugs. The current study presents a 5-year-old male with a previous diagnosis of systemic-onset juvenile idiopathic arthritis (SoJIA) and macrophage-activation syndrome who developed posterior reversible encephalopathy syndrome during treatment with glucocorticoids, disease-modifying antirheumatic drugs and biological agent (etanercept) therapy. After ~5 days of treatment, the patient made a complete clinical recovery; the magnetic resonance imaging reviewed 2 weeks later showed that the previous hyper-intensity signal had disappeared and the multiple lesions in the brain had been completely absorbed. The case report shows that, conforming to recent literature, SoJIA in infants should be considered a risk factor for developing RPLS. The clinical manifestations of the disease are multiple, but usually reversible, and the patients mostly have a good prognosis. Rapid diagnosis and treatment is essential as early treatment may prevent progression to irreversible brain damage. By increasing the awareness of RPLS, the patient care may improve and further insight may be gained.

Dual pathology: cervicofacial actinomycosis and nicorandil-induced oral ulceration.

PubMed

Cupples, H E V; McGahey, D T

2008-04-01

Oral ulceration has many causes and is a common presenting symptom in otolaryngology. This article presents an unusual case of dual pathology oral ulceration in an elderly patient. Oral malignancy was initially suspected, but the history, examination and investigation showed that the oral ulceration was caused by actinomycosis infection and by nicorandil use. Cervicofacial acinomycosis is a rare, suppurative bacterial disease in which abscesses can form in the tissues and break through the skin, creating pus-discharging lesions. Nicorandil is a potassium channel blocker used in the treatment of ischaemic heart disease. It has been recently recognised as a cause of persistent ulcerative stomatitis. This case highlights the importance of a high index of suspicion for unusual and reversible causes of oral ulceration, and of dual pathology as a cause. Such vigilance enables early recognition and treatment of potentially reversible conditions.

Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

PubMed

Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.

Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats

PubMed Central

Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME. PMID:27627764

In Situ complement activation and T-cell immunity in leprosy spectrum: An immunohistological study on leprosy lesional skin.

PubMed

Bahia El Idrissi, Nawal; Iyer, Anand M; Ramaglia, Valeria; Rosa, Patricia S; Soares, Cleverson T; Baas, Frank; Das, Pranab K

2017-01-01

Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition worsens often during and long after treatment. Clearance of bacterial antigens including lipoarabinomannan (LAM) during and after treatment in leprosy patients is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves by in situ generation of the membrane attack complex (MAC). Investigating the role of complement activation in skin lesions of leprosy patients might provide insight into the dynamics of in situ immune reactivity and the destructive pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy patients, whether M. leprae antigen LAM deposition correlates with the deposition of complement activation products MAC and C3d on nerves and cells in the surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n = 6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The percentage of C3d, MAC and LAM deposition was significantly higher in the skin biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p = <0.001 and p = <0.001 respectively), with a significant association between LAM and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001 and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary patients, MAC deposition was found on axons and co-localizing with LAM. In skin lesions of paucibacillary patients, we found C3d positive T-cells in and surrounding granulomas, but hardly any MAC deposition. In addition, MAC immunoreactivity was increased in both ENL and RR skin lesions compared to non-reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present findings demonstrate that complement is deposited in skin lesions of leprosy patients, suggesting that inflammation driven by complement activation might contribute to nerve damage in the lesions of these patients. This should be regarded as an important factor in M. leprae nerve damage pathology.

Resolution of brainstem edema after treatment of a dural tentorial arteriovenous fistula.

PubMed

Alvarez, Hortensia; Sasaki-Adams, Deanna; Castillo, Mauricio

2015-10-01

We report a patient with a petrosal arterio-venous dural fistula draining into the ponto-mesencephalic and medullary venous systems presenting with edema of the brain stem and complete reversal of magnetic resonance imaging (MRI) abnormalities after combined endovascular and surgical treatments. The venous anatomy of the posterior fossa and the significance of the venous involvement as the cause of clinical symptoms and imaging abnormalities in cerebro-medullary vascular lesions are discussed. © The Author(s) 2015.

Clinical experience with iodine-123-iodophenylpentadecanoic acid.

PubMed

Corbett, J

1994-04-01

Initial research in dogs and later research in normal volunteers and patients with coronary artery disease indicated that 123I-iodophenylpentadecanoic acid (IPPA) can provide valuable diagnostic information. This agent compared favorably to 201Tl in detecting stenosed coronary arteries and identified reversible lesions with greater frequency. Testing with both 201Tl and IPPA before and after percutaneous transluminal coronary angioplasty produced similar results, supporting the notion that IPPA deserves inclusion among the diagnostic tools used to evaluate coronary heart disease.

Early dissemination seeds metastasis in breast cancer

PubMed Central

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

[Expression of gamma interferon during HPV and Chlamydia trachomatis infection in cervical samples].

PubMed

Colín-Ferreyra, María Del Carmen; Mendieta-Zerón, Hugo; Romero-Figueroa, María Del Socorro; Martínez-Madrigal, Migdania; Martínez-Pérez, Sergio; Domínguez-García, María Victoria

2015-02-01

The aim of this study was to mesure the expression of gamma interferon in HPV and Chlamydia trachomatis infection in squamous intraepithelial lesions. Samples from 100 patients diagnosed by colposcopy with or without squamous intraepithelial lesions were used in the present study. Each patient was found to be infected by HPV and C.trachomatis. Relative gamma interferon mRNA expression was assessed using a real-time reverse transcriptase PCR assay (RT-PCR). The relative units of expression of gamma interferon mRNA were 13, 1.8 and 0.3, for HPV and C.trachomatis co-infection, or HPV or C.trachomatis infection, respectively. HPV and C.trachomatis could overstimulate the expression of gamma interferon. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The Immunology of AD and its Reversibility with Broad Spectrum and Targeted Therapies

PubMed Central

Brunner, Patrick M.; Guttman-Yassky, Emma; Leung, Donald Y. M.

2017-01-01

Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of Th22, Th17/IL-23 and Th1 cytokine pathways, depending on the subtype of the disease. In this review, we discuss our current understanding of the AD immune map in both early-onset as well as chronic disease. Clinical studies using broad and targeted therapeutics have helped to elucidate the contribution of various immune axes to the disease phenotype. Importantly, immune activation extends well beyond lesional AD, as non-lesional skin and the blood component harbor AD-specific inflammatory changes. For this reason, future therapeutics will need to focus on a systemic treatment approach, especially in patients suffering from moderate-to-severe disease. PMID:28390479

Caries Detection Methods Based on Changes in Optical Properties between Healthy and Carious Tissue

PubMed Central

Karlsson, Lena

2010-01-01

A conservative, noninvasive or minimally invasive approach to clinical management of dental caries requires diagnostic techniques capable of detecting and quantifying lesions at an early stage, when progression can be arrested or reversed. Objective evidence of initiation of the disease can be detected in the form of distinct changes in the optical properties of the affected tooth structure. Caries detection methods based on changes in a specific optical property are collectively referred to as optically based methods. This paper presents a simple overview of the feasibility of three such technologies for quantitative or semiquantitative assessment of caries lesions. Two of the techniques are well-established: quantitative light-induced fluorescence, which is used primarily in caries research, and laser-induced fluorescence, a commercially available method used in clinical dental practice. The third technique, based on near-infrared transillumination of dental enamel is in the developmental stages. PMID:20454579

A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.

PubMed

Sikiric, P; Marovic, A; Matoz, W; Anic, T; Buljat, G; Mikus, D; Stancic-Rokotov, D; Separovic, J; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Zoricic, I; Turkovic, B; Aralica, G; Perovic, D; Duplancic, B; Lovric-Bencic, M; Rotkvic, I; Mise, S; Jagic, V; Hahn, V

1999-12-01

The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP.

Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.

PubMed

Kappus, Mojdeh S; Murphy, Andrew J; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L; Tall, Alan R; Westerterp, Marit

2014-02-01

Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate reverse cholesterol transport, would abolish the beneficial effects of LXR activation on atherosclerosis. LXR activator T0901317 substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-) mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM) and fed a Western-type diet for 6 weeks with or without T0901317 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0901317 markedly decreased lesion area, complexity, and inflammatory cell infiltration in the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western-type diet with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups, and the decrease was more prominent in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. The results suggest that anti-inflammatory effects of LXR activators are of key importance to their antiatherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to transrepress inflammatory genes.

The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model

PubMed Central

Geis, Christian; Ritter, Christian; Ruschil, Christoph; Weishaupt, Andreas; Grünewald, Benedikt; Stoll, Guido; Holmoy, Trygve; Misu, Tatsuro; Fujihara, Kazuo; Hemmer, Bernhard; Stadelmann, Christine; Bennett, Jeffrey L.; Sommer, Claudia; Toyka, Klaus V.

2015-01-01

Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was down-regulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of “penumbra-like” lesions recently reported in NMO patients adjacent to effector-mediated tissue damage. PMID:25542977

The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model.

PubMed

Geis, Christian; Ritter, Christian; Ruschil, Christoph; Weishaupt, Andreas; Grünewald, Benedikt; Stoll, Guido; Holmoy, Trygve; Misu, Tatsuro; Fujihara, Kazuo; Hemmer, Bernhard; Stadelmann, Christine; Bennett, Jeffrey L; Sommer, Claudia; Toyka, Klaus V

2015-03-01

Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was downregulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of "penumbra-like" lesions recently reported in NMO patients adjacent to effector-mediated tissue damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Human scavenger receptor class B type I is expressed with cell-specific fashion in both initial and terminal site of reverse cholesterol transport.

PubMed

Nakagawa-Toyama, Yumiko; Hirano, Ken-ichi; Tsujii, Ken-ichi; Nishida, Makoto; Miyagawa, Jun-ichiro; Sakai, Naohiko; Yamashita, Shizuya

2005-11-01

The reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis, in which high-density lipoprotein (HDL) removes cholesterol from lipid-laden cells and delivers it to the liver. Scavenger receptor class B type I (SR-BI) is a HDL receptor in the liver and adrenal glands and is involved in the selective uptake of cholesteryl ester from HDL, which has been extensively, analyzed using rodent models. However, the expression and regulation of the human homologue of this receptor are not known yet. We previously reported that this receptor is expressed in in vitro differentiated macrophages and its expression is up-regulated by the addition of modified lipoproteins into the medium [Hirano K, Yamashita S, Nakagawa Y, et al. Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions. Circ Res 1999;85:108-16]. In order to further investigate the physiological significance of this receptor in humans, we have performed extensive immunohistochemical analyses with specimens of the liver and adrenal glands as well as arteries with different stages of atherosclerotic lesions. In human liver and adrenal glands, a positive SR-BI immunoreactivity was detected in both hepatic and adrenal parenchymal cells as well as Kupffer cells. These parenchymal cells had a strong signal on the cell surface, whereas Kupffer cells showed a heterogeneous and punctate pattern. In human aorta and coronary arteries, SR-BI was highly expressed in atherosclerotic plaques, but not in non-atherosclerotic lesions. Double immunostaining revealed that SR-BI was expressed in a subpopulation of macrophages, of which staining pattern was similar to that observed in Kupffer cells. These data clearly demonstrated that SR-BI was expressed with cell-specific fashions in both the initial and terminal step of RCT in humans. Thus, SR-BI might be physiologically relevant and have distinct tissue-specific functions.

Coronavirus infection in intensively managed cattle with respiratory disease.

PubMed

Hick, P M; Read, A J; Lugton, I; Busfield, F; Dawood, K E; Gabor, L; Hornitzky, M; Kirkland, P D

2012-10-01

A detailed laboratory investigation identified bovine coronavirus (BCoV) as the aetiological agent in an outbreak of respiratory disease at a semi-intensive beef cattle feedlot in south-east Australia. The outbreak caused 30% morbidity in the resident population and also affected two cohorts of cattle that were newly introduced to the property. At slaughter, pulmonary consolidation and inflammatory lesions in the trachea were identified in 15 of 49 animals. Pasteurella multocida or Histophilus somni was cultured from 3 of 7 animals with lesions. Histopathological examination revealed multifocal non-suppurative bronchointerstitial pneumonia with formation of epithelial syncytial cells, sometimes associated with suppurative bronchopneumonia. BCoV was detected in nasal swabs and pulmonary lesions using real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay and virus isolation. There was serological evidence of previous exposure to bovine viral diarrhoea virus, bovine respiratory syncytial virus and bovine parainfluenza virus type 3, but not to bovine herpesvirus type 1. None of these viral pathogens or Mycoplasma bovis was identified by qRT-PCR. This is believed to be the first report of BCoV in association with bovine respiratory disease complex in Australia. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Feeding-produced subchronic high plasma levels of uric acid improve behavioral dysfunction in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

PubMed

Nakashima, Akio; Yamauchi, Atsushi; Matsumoto, Junichi; Dohgu, Shinya; Takata, Fuyuko; Koga, Mitsuhisa; Fukae, Jiro; Tsuboi, Yoshio; Kataoka, Yasufumi

2018-05-25

The development of Parkinson's disease (PD) involves the degeneration of dopaminergic neurons caused by oxidative stress. Accumulating clinical evidence indicates that high blood levels of uric acid (UA), an intrinsic antioxidative substance, are associated with reduced risk of PD. However, this hypothesis has not been confirmed by in-vivo experiments. The present study investigated the effects of UA on behavioral abnormalities in the development of PD. We used unilateral 6-hydroxydopamine-lesioned mice, which were fed on a diet containing 1% UA and 2.5% potassium oxonate (an uricase inhibitor) to induce hyperuricemia. A significant elevation in UA levels was found in groups that were fed a UA diet. The 6-hydroxydopamine-lesioned mice showed impaired rotarod performance and increased apomorphine-induced contralateral rotations. These behavioral abnormalities were significantly reversed by feeding a UA diet for 1 week before and 5 weeks after surgery (subchronic hyperuricemia). These behavioral improvements occurred in parallel with recovery of tyrosine hydroxylase protein levels in the lesioned striatal side. The present study with a dietary hyperuricemia mice model confirms that UA exerts a neuroprotective effect on dopaminergic neuronal loss, improving motor dysfunction and ameliorating PD development.

A clinical investigation of the efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride, as sodium monofluorophosphate in a calcium base, on primary root caries.

PubMed

Hu, D Y; Yin, W; Li, X; Feng, Y; Zhang, Y P; Cummins, D; Mateo, L R; Ellwood, R P

2013-01-01

The purpose of this six-month study was to assess the ability of a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate, to arrest and reverse primary root caries lesions in adults. Three test groups used dentifrices which contained either: 1) 1.5% arginine and 1450 ppm fluoride as sodium monofluorophosphate in a calcium base (experimental); 2) 1450 ppm fluoride as sodium fluoride in a silica base (positive control); or 3) no fluoride in a calcium base (negative control). The study participants were residents of the city of Chengdu, Sichuan Province, China. In order to take part, subjects had to have at least one non-cavitated primary root caries lesion. A total of 412 subjects completed the study. They were aged from 50 to 70 years (mean age 64 +/- 4.1 years) and 53.6% were female. Efficacy for arresting and reversal of primary root caries was assessed by clinical hardness measures and through the use of the Electrical Caries Monitor. After three months of product use, clinical hardness measures showed that 27.7%, 24.6%, and 13.1% of lesions had improved in the experimental, positive, and negative control groups, respectively, and 0.7%, 4.5%, and 16.8% had become worse, respectively. The differences in the distribution of lesion change between the negative control group and both the experimental (p < 0.001) and positive control (p = 0.001) were statistically significant. The Electrical Caries Monitor was also used as an objective measure of lesion severity. The end values increased from baseline to the three-month examinations, but none of the differences between the groups attained statistical significance. After six months, clinical hardness measures showed that only one lesion (0.7%) was worse than at the baseline examination-in the experimental group compared to 9.0% and 18.2% in the positive and negative control groups, respectively. In addition, 61.7%, 56.0%, and 27.0%, respectively, showed improvement for the three groups. The differences in the distribution of lesion change scores between the negative control group and both the experimental (p < 0.001) and positive control (p < 0.001) were statistically significant, as was the difference between the experimental group and the positive control (p = 0.006). The Electrical Caries Monitor end values for the experimental, positive, and negative control groups at the six-month examination were 7.9, 1.9 mega omega(s), and 387 kilo omegas(s), respectively. The differences between the negative control group and both the experimental (p < 0.001) and positive control (p < 0.001) were statistically significant. The difference between the experimental and positive control groups was also statistically significant (p = 0.03). It is concluded that the new toothpaste containing 1.5% arginine and 1450 ppm fluoride, as sodium monofluorophosphate in a calcium base, provided greater anticaries benefits than a conventional toothpaste containing 1450 ppm fluoride. Both fluoride toothpastes demonstrated greater benefits than non-fluoride toothpaste.

Reverse Dynamization: Influence of Fixator Stiffness on the Mode and Efficiency of Large-Bone-Defect Healing at Different Doses of rhBMP-2.

PubMed

Glatt, Vaida; Bartnikowski, Nicole; Quirk, Nicholas; Schuetz, Michael; Evans, Christopher

2016-04-20

Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions. Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing. In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification. These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully. Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

The Metabotropic Glutamate Receptor 4-Positive Allosteric Modulator VU0364770 Produces Efficacy Alone and in Combination with l-DOPA or an Adenosine 2A Antagonist in Preclinical Rodent Models of Parkinson's Disease

PubMed Central

Jones, Carrie K.; Bubser, Michael; Thompson, Analisa D.; Dickerson, Jonathan W.; Turle-Lorenzo, Nathalie; Amalric, Marianne; Blobaum, Anna L.; Bridges, Thomas M.; Morrison, Ryan D.; Jadhav, Satyawan; Engers, Darren W.; Italiano, Kimberly; Bode, Jacob; Daniels, J. Scott; Lindsley, Craig W.; Hopkins, Corey R.; Conn, P. Jeffrey

2012-01-01

Parkinson's disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu4), including N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclinical models of PD. However, these early mGlu4 PAMs exhibited unsuitable physiochemical properties for systemic dosing, requiring intracerebroventricular administration and limiting their broader utility as in vivo tools to further understand the role of mGlu4 in the modulation of basal ganglia function relevant to PD. In the present study, we describe the pharmacologic characterization of a systemically active mGlu4 PAM, N-(3-chlorophenyl)picolinamide (VU0364770), in several rodent PD models. VU0364770 showed efficacy alone or when administered in combination with l-DOPA or an adenosine 2A (A2A) receptor antagonist currently in clinical development (preladenant). When administered alone, VU0364770 exhibited efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6-hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhanced the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry were also potentiated when the compound was coadministered with an inactive dose of l-DOPA, suggesting that mGlu4 PAMs may provide l-DOPA-sparing activity. The present findings provide exciting support for the potential role of selective mGlu4 PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either l-DOPA or A2A antagonists. PMID:22088953

Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.

PubMed

Viswanathan, Preeti; Sharma, Yogeshwar; Gupta, Priya; Gupta, Sanjeev

2018-03-05

Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures. In experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling. Cell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure. © 2018 John Wiley & Sons Ltd.

Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.

PubMed

Wang, P-H; Ko, J-L

2006-01-01

The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P < 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.

Clinical and Imaging Findings in Childhood Posterior Reversible Encephalopathy Syndrome

PubMed Central

GUNGOR, Serdal; KILIC, Betul; TABEL, Yilmaz; SELIMOGLU, Ayse; OZGEN, Unsal; YILMAZ, Sezai

2018-01-01

Objective Posterior reversible encephalopathy syndrome (PRES) is characterized by typical radiologic findings in the posterior regions of the cerebral hemispheres and cerebellum. The symptoms include headache, nausea, vomiting, visual disturbances, focal neurologic deficits, and seizures. The aim of this study is to evaluate the clinical and radiological features of PRES in children and to emphasize the recognition of atypical features. Materials & Methods We retrospectively examined 23 children with PRES from Mar 2010-Apr 2015 in Inonu University Turgut Ozal Medical Center in Turkey. We compared the clinical features and cranial MRI findings between underlying diseases of PRES. Results The most common precipitating factors were hypertension (78.2%) and medications, namely immunosuppressive and antineoplastic agents (60.8%). Manifestations included mental changes (100%), seizures (95.6%), headache (60.8%), and visual disturbances (21.7%) of mean 3.6 (range 1-10) days' duration. Cranial magnetic resonance imaging (MRI) showed bilateral occipital lesions in all patients, associated in 82.6% with less typical distribution of lesions in frontal, temporal or parietal lobes, cerebellum, corpus callosum, basal ganglia, thalamus, and brain stem. Frontal involvement was predominant, observed in 56.5% of patients. Clinical recovery was followed by radiologic resolution in all patients. Conclusion PRES is often unsuspected by the clinician, thus radiologists may be the first to suggest this diagnosis on an MRI obtained for seizures or encephalopathy. Atypical MRI finding is seen quite often. Rapid diagnosis and treatment are required to avoid a devastating outcome. PMID:29379559

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

PubMed Central

Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Ablonczy, Zsolt; Hafezi-Moghadam, Ali

2009-01-01

Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 μmol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP’s effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP’s TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy. PMID:19910509

Oxygen, the lung and the diver: friends and foes?

PubMed

van Ooij, Pieter-Jan A M; Sterk, Peter J; van Hulst, Robert A

2016-12-01

Worldwide, the number of professional and sports divers is increasing. Most of them breathe diving gases with a raised partial pressure of oxygen (P O 2 ). However, if the P O 2 is between 50 and 300 kPa (375-2250 mmHg) (hyperoxia), pathological pulmonary changes can develop, known as pulmonary oxygen toxicity (POT). Although in its acute phase, POT is reversible, it can ultimately lead to non-reversible pathological changes. Therefore, it is important to monitor these divers to prevent them from sustaining irreversible lesions.This review summarises the pulmonary pathophysiological effects when breathing oxygen with a P O 2 of 50-300 kPa (375-2250 mmHg). We describe the role and the limitations of lung function testing in monitoring the onset and development of POT, and discuss new techniques in respiratory medicine as potential markers in the early development of POT in divers. Copyright ©ERS 2016.

Progressive renal insufficiency related to ALK inhibitor, alectinib.

PubMed

Nagai, Kojiro; Ono, Hiroyuki; Matsuura, Motokazu; Hann, Michael; Ueda, Sayo; Yoshimoto, Sakiya; Tamaki, Masanori; Murakami, Taichi; Abe, Hideharu; Ishikura, Hisashi; Doi, Toshio

2018-04-01

Alectinib is a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor and is generally effective and tolerated in patients who have demonstrated disease progression or adverse effects while on the first generation inhibitor, crizotinib. ALK inhibitors can cause a reversible chronic increase of serum creatinine concentration; however, they rarely induce progressive renal insufficiency. We herein report a case of a 68-year-old woman diagnosed with ALK-positive advanced non-small cell lung cancer and who received ALK inhibitors. Due to dysgeusia and transaminitis, her medication was switched from crizotinib to alectinib. Rapid progressive glomerulonephritis developed 1 year after the initiation of alectinib treatment. A renal biopsy revealed unique kidney lesions in both tubules and glomeruli. Glucocorticoid therapy partially reversed kidney impairment. However, re-administration of alectinib caused kidney dysfunction, which was improved by the cessation of alectinib. Our case suggests that much attention should be paid to kidney function when using ALK inhibitors.

Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction

PubMed Central

Chen, Jeremy Tsung-chieh; Guo, Da; Campanelli, Dario; Frattini, Flavia; Mayer, Florian; Zhou, Luming; Kuner, Rohini; Heppenstall, Paul A.; Knipper, Marlies; Hu, Jing

2014-01-01

The gate control theory proposes the importance of both pre- and post-synaptic inhibition in processing pain signal in the spinal cord. However, although postsynaptic disinhibition caused by brain-derived neurotrophic factor (BDNF) has been proved as a crucial mechanism underlying neuropathic pain, the function of presynaptic inhibition in acute and neuropathic pain remains elusive. Here we show that a transient shift in the reversal potential (EGABA) together with a decline in the conductance of presynaptic GABAA receptor result in a reduction of presynaptic inhibition after nerve injury. BDNF mimics, whereas blockade of BDNF signalling reverses, the alteration in GABAA receptor function and the neuropathic pain syndrome. Finally, genetic disruption of presynaptic inhibition leads to spontaneous development of behavioural hypersensitivity, which cannot be further sensitized by nerve lesions or BDNF. Our results reveal a novel effect of BDNF on presynaptic GABAergic inhibition after nerve injury and may represent new strategy for treating neuropathic pain. PMID:25354791

Reversible Holmes' tremor due to spontaneous intracranial hypotension.

PubMed

Iyer, Rajesh Shankar; Wattamwar, Pandurang; Thomas, Bejoy

2017-07-27

Holmes' tremor is a low-frequency hand tremor and has varying amplitude at different phases of motion. It is usually unilateral and does not respond satisfactorily to drugs and thus considered irreversible. Structural lesions in the thalamus and brainstem or cerebellum are usually responsible for Holmes' tremor. We present a 23-year-old woman who presented with unilateral Holmes' tremor. She also had hypersomnolence and headache in the sitting posture. Her brain imaging showed brain sagging and deep brain swelling due to spontaneous intracranial hypotension (SIH). She was managed conservatively and had a total clinical and radiological recovery. The brain sagging with the consequent distortion of the midbrain and diencephalon was responsible for this clinical presentation. SIH may be considered as one of the reversible causes of Holmes' tremor. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5 in human atherectomy specimens.

PubMed

Grant, M B; Wargovich, T J; Ellis, E A; Tarnuzzer, R; Caballero, S; Estes, K; Rossing, M; Spoerri, P E; Pepine, C

1996-12-17

The molecular and cellular processes that induce rapid atherosclerotic plaque progression in patients with unstable angina and initiate restenosis following coronary interventional procedures are uncertain. We examined primary (de novo) and restenotic lesions retrieved at the time of directional coronary atherectomy for expression of insulin-like-growth factor-I (IGF-I). IGF-I receptor, and five IGF binding proteins (IGFBPs), IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 in smooth muscle cells (SMCs) using colloidal gold immunocytochemistry. IGF-1, its receptor and binding proteins were not detected in SMCs of normal coronary arteries. IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in both de novo and restenotic plaques. IGF-I receptor localized on sSMCs and their processes and colocalized with IGF-I. Although morphometric analysis of IGF-I and IGF-I receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed comparable levels of IGF-I (3.2 +/- 1.0 and 2.9 +/- 0.9, respectively). IGF-I receptor was significantly higher in de novo lesions as compared to restenotic lesions (10.7 +/- 2.5 and 4.2 +/- 1.3, P < 0.05, respectively). IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5 localized in the cytoplasm of sSMCs and in the extracellular matrix. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) performed on de novo atherectomy specimens identified mRNA for IGF-I, IGF-I receptor, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 levels and detected mRNA for IGFBP-3. The expression of IGF-I, IGF-I receptor, and IGFBPs in atherectomy plaques suggests that the development of coronary obstructive lesions may be a result of changes in the IGF system.

Safety Outcomes Using a Proximal Protection Device in Carotid Stenting of Long Carotid Stenoses

PubMed Central

Atchaneeyasakul, Kunakorn; Khandelwal, Priyank; Ambekar, Sudheer; Ramdas, Kevin; Guada, Luis; Yavagal, Dileep

2016-01-01

Background Embolic protection devices can prevent atherosclerotic emboli during carotid stenting. Newer proximal protection devices reverse flow in the internal carotid artery (ICA), leading to reduction in perioperative microemboli. The risk of stroke is high for carotid stenting of ICA lesions with a length >10 mm and/or angiographic string sign. Objective We aimed to evaluate the safety outcomes of proximal embolic protection device usage in this high-risk group. Methods This is a retrospective analysis of patients who underwent carotid stenting procedures with proximal embolic protection devices at a tertiary care center. High-risk features for adverse events with carotid stenting were identified. Peri- and postprocedural outcomes were recorded. We further compared outcomes in patients with a carotid stenosis length >10 mm to those with shorter stenosis. Results From January 2011 to December 2014, we included 27 patients; 96.3% were symptomatic and 3.7% were asymptomatic. There was a stent placement technical success rate of 100%. No major stroke or coronary events were recorded. One minor stroke event developed in one patient. A carotid lesion length >10 mm and/or angiographic string sign was noted in 21/27 patients, with an average lesion length of 14.4 mm. One patient (4.8%) in this group developed a minor stroke event. Neither a coronary nor a major stroke event was recorded in this group. There was no significant difference in the complication rate between the long lesion and the control group. Conclusion In our patient cohort, it was found that a proximal embolic protection device is safe for patients with carotid stenosis, including those with a carotid lesion length >10 mm and/or angiographic string sign. PMID:27781040

[Preventive and remineralization effect over incipient lesions of caries decay by phosphopeptide-amorphous calcium phosphate].

PubMed

Juárez-López, María Lilia Adriana; Hernández-Palacios, Rosa Diana; Hernández-Guerrero, Juan Carlos; Jiménez-Farfán, Dolores; Molina-Frechero, Nelly

2014-01-01

INTRODUCTION. Dental caries continues to affect a large percentage of Mexican children and currently advises that if diagnosed at an early stage can be reversed with minimally invasive treatments. The casein phosphopeptide amorphous calcium phosphate known as CPP-ACP is a phosphoprotein capable of releasing calcium and phosphate ions in the oral environment promoting remineralization. OBJECTIVE. To evaluate the effect of CPP-ACP with fluoride added in a scholar preventive program. MATERIAL AND METHODS. A cuasi- experimental study was conducted in 104 schools of six years old. The children were classified into three groups and received six months biweekly applications of different treatments: casein phosphopeptide amorphous calcium phosphate added fluoride (CPP-ACPF), sodium fluoride (NaF) and a control group. Clinical evaluation was performed with the laser fluorescence technique (Diagnodent model 2095). 1340 teeth were included: 294 teeth with incipient lesions and 1,046 healthy teeth. Statistical tests of χ2 y Mc Nemar were used. RESULTS. In the group that received the application of CPP-ACPF, 38% of incipient carious lesions were remineralizing compared with 21% in the group receiving the NaF (p < 0.001) and 15% in the control group (p < 0.0001) The percentage of teeth free of caries were preserved in the therapy group phosphoprotein was the biggest. This group also showed the lower proportion of deep carious lesion development (p < 0.0001). CONCLUSION. The application biweekly for six months of CPP-ACPF showed a protective and remineralizing effect on incipient carious lesions. His action was better than the application of NaF. However, to reduce the impact from dental caries in schoolchildren is important to have a comprehensive preventive approach that includes promoting self-care, as well as the application of sealants.

Bisphenol A Promotes Cell Survival Following Oxidative DNA Damage in Mouse Fibroblasts

PubMed Central

Gassman, Natalie R.; Coskun, Erdem; Stefanick, Donna F.; Horton, Julie K.; Jaruga, Pawel; Dizdaroglu, Miral; Wilson, Samuel H.

2015-01-01

Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway. PMID:25693136

High-frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease.

PubMed

Li, Xiang-Hong; Wang, Jin-Yan; Gao, Ge; Chang, Jing-Yu; Woodward, Donald J; Luo, Fei

2010-05-15

Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico-basal ganglia circuits. (c) 2009 Wiley-Liss, Inc.

TRB3 is elevated in psoriasis vulgaris lesions and mediates HaCaT cells proliferation in vitro.

PubMed

Yu, Xiao-Jing; Song, Tie-Jun; Zhang, Lu-Wei; Su, Ying; Wang, Ke-Yu; Sun, Qing

2017-10-01

Psoriasis is a chronic skin disease characterized by abnormal keratinocyte proliferation and differentiation, inflammation, and angiogenesis. Overexpression of tribbles homolog3 (TRB3), which belongs to the tribbles family of pseudokinases, has been found in several human tumors and metabolic diseases, but its role in psoriasis has not been fully clarified. The aim of this study is to investigate the expression of TRB3 in psoriasis and explore its roles in the proliferation of keratinocytes. Twenty-four patients with psoriasis vulgaris were recruited for the study. Diagnosis of psoriasis was based on clinical and histologic examinations. Immunohistochemistry and real-time reverse transcription PCR (RT-PCR) were performed to determine protein and messenger RNA (mRNA) expression of TRB3 in psoriasis lesions. 5-Bromo-2-deoxyUridine (BrdU) incorporation assay were performed for cell proliferation. Cell cycle distribution was assessed by flow cytometry analysis. The levels of TRB3 is elevated in psoriatic lesions compared with psoriatic non-lesions. The HaCat cells expressed the TRB3 gene. We found TRB3 silencing to significantly inhibit HaCat cell proliferation. Furthermore, the specific knockdown of TRB3 slowed down the cell cycle at the gap 0/first gap phase. In conclusion, our data suggest that TRB3 is overexpressed in lesions of patients with psoriasis and may be involved in the abnormal proliferation of keratinocytes. Therefore, TRB3 may be a potential therapeutic target for psoriasis. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protective effect of lafutidine, a histamine H2 receptor antagonist, against loxoprofen-induced small intestinal lesions in rats.

PubMed

Amagase, Kikuko; Ochi, Akimu; Sugihara, Tetsuya; Kato, Shinichi; Takeuchi, Koji

2010-05-01

We examined the effect of lafutidine, a histamine H(2) receptor antagonist with a mucosal protective action mediated by capsaicin-sensitive sensory neurons (CSN), on intestinal lesions produced by loxoprofen administration in rats. Animals were given loxoprofen (10-100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16-dimethyl prostaglandin E(2) (dmPGE(2); 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after. Loxoprofen dose-dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine (30 mg/kg), similar to dmPGE(2) and ampicillin, and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN. Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.

Tet methylcytosine dioxygenase 2 inhibits atherosclerosis via upregulation of autophagy in ApoE−/− mice

PubMed Central

Peng, Juan; Yang, Qin; Li, A-Fang; Li, Rong-Qing; Wang, Zuo; Liu, Lu-Shan; Ren, Zhong; Zheng, Xi-Long; Tang, Xiao-Qing; Li, Guo-Hua; Tang, Zhi-Han; Jiang, Zhi-Sheng; Wei, Dang-Heng

2016-01-01

Tet methylcytosine dioxygenase 2 (TET2) mediates the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). The loss of TET2 is associated with advanced atherosclerotic lesions. Our previous study showed that TET2 improves endothelial cell function by enhancing endothelial cell autophagy. Accordingly, this study determined the role of TET2 in atherosclerosis and potential mechanisms. In ApoE−/− mice fed high-fat diet, TET2 overexpression markedly decreased atherosclerotic lesions with uniformly increased level of 5hmC and decreased level of 5mC in genomic DNA. TET2 overexpression also promoted autophagy and downregulated inflammation factors, such as vascular cell adhesion molecule 1, intercellular adhesion molecule 1, monocyte chemotactic protein 1, and interleukin-1. Consistently, TET2 knockdown with small hairpin RNA (shRNA) in ApoE−/− mice decreased 5hmC and increased 5mC levels in atherosclerotic lesions. Meanwhile, autophagy was inhibited and atherosclerotic lesions progressed with an unstable lesion phenotype characterized by large lipid core, macrophage accumulation, and upregulated inflammation factor expression. Experiments with the cultured endothelial cells revealed that oxidized low-density lipoprotein (ox-LDL) inhibited endothelial cell autophagy. TET2 shRNA strengthened impaired autophagy and autophagic flux in the ox-LDL-treated endothelial cells. TET2 overexpression reversed these effects by decreasing the methylation level of the Beclin 1 promoter, which contributed to the downregulation of inflammation factors. Overall, we identified that TET2 was downregulated during the pathogenesis of atherosclerosis. The downregulation of TET2 promotes the methylation of the Beclin 1 promoter, leading to endothelial cell autophagy, impaired autophagic flux, and inflammatory factor upregulation. Upregulation of TET2 may be a novel therapeutic strategy for treating atherosclerosis. PMID:27821816

Lipoid proteinosis: A case with distinct histopathological and radiological findings.

PubMed

Brar, Balvinder Kaur; Jain, Sarina; Brar, Sukhmani Kaur

2017-10-01

Lipoid proteinosis is a rare inherited genodermatosis characterized by hyaline deposits in various tissues. Clinically, it manifests with cutaneous as well as extracutaneous features. Periodic acid-Schiff (PAS)-reactive hyaline deposits in the upper dermis, with localization around blood vessels and eccrine sweat glands, in particular, is the histopathological hallmark finding. On brain imaging, bilateral symmetrical temporal lobe calcifications are considered to be pathognomonic of this disorder. We report a case of lipoid proteinosis in which hyaline deposits were present in the papillary and reticular dermis, without being seen at the periphery of eccrine sweat glands, along with dystrophic calcification. Magnetic resonance imaging (MRI) of brain revealed hydrocephalus, subependymal heterotropia and absent splenium of corpus callosum with no evidence of temporal lobe calcification. Thus, our case highlights the inherent diverse nature of lipoid proteinosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A case of hypoglycemic hemiparesis and literature review

PubMed Central

Meguro, Shu; Soeda, Yukie; Itoh, Arata; Kawai, Toshihide; Itoh, Hiroshi

2012-01-01

An 89-year-old man with diabetes treated with metformin 500 mg/day and glimepiride 4 mg/day was hospitalized because of hypoglycemic right hemiparesis and dysarthria (casual glucose value 1.8 mmol/L), which resolved quickly following administration of 40 mL of 40% dextrose. Hemiparesis is a rare symptom (4.2%) of hypoglycemia. There are about 200 case reports of hypoglycemic hemiparesis. The average glucose level at which hemiparesis developed was 1.8 mmol/L. Right-sided hemiparesis predominated (R 66%; L 34%). On imaging studies, abnormal findings were frequently observed in the internal capsule or splenium of the corpus callosum. The mechanism of hemiparesis is not fully understood. The existence of cases in which hypoglycemia cannot be distinguished from stroke on imaging studies suggests the importance of measurement of the blood glucose level when the symptoms of stroke are first recognized. PMID:22247979

A case of hypoglycemic hemiparesis and literature review.

PubMed

Yoshino, Tetsuhiro; Meguro, Shu; Soeda, Yukie; Itoh, Arata; Kawai, Toshihide; Itoh, Hiroshi

2012-08-01

An 89-year-old man with diabetes treated with metformin 500 mg/day and glimepiride 4 mg/day was hospitalized because of hypoglycemic right hemiparesis and dysarthria (casual glucose value 1.8 mmol/L), which resolved quickly following administration of 40 mL of 40% dextrose. Hemiparesis is a rare symptom (4.2%) of hypoglycemia. There are about 200 case reports of hypoglycemic hemiparesis. The average glucose level at which hemiparesis developed was 1.8 mmol/L. Right-sided hemiparesis predominated (R 66%; L 34%). On imaging studies, abnormal findings were frequently observed in the internal capsule or splenium of the corpus callosum. The mechanism of hemiparesis is not fully understood. The existence of cases in which hypoglycemia cannot be distinguished from stroke on imaging studies suggests the importance of measurement of the blood glucose level when the symptoms of stroke are first recognized.

DTI-MRI biomarkers in the search for normal pressure hydrocephalus aetiology: a review.

PubMed

Hoza, David; Vlasák, Aleš; Hořínek, Daniel; Sameš, Martin; Alfieri, Alex

2015-04-01

Normal pressure hydrocephalus (NPH) is a clinical syndrome characterized by gait disturbances, urinary incontinence and dementia. Clinical presentation overlaps with Alzheimer disease (AD). Early recognition thus early intervention (shunting) is important for successful treatment, but lack of a diagnostic test with sufficient sensitivity and specificity complicates the diagnosis. We performed literature search and composed a structured review of imaging biomarkers of NPH. Morphometric studies are not sufficient to diagnose NPH. Hydrocephalus is a common finding in elderly people due to the symmetric brain atrophy and is even more pronounced in patients with AD. The key MRI biomarker seems to be diffusion tensor imaging (DTI). According to recent studies, the DTI analysis of the splenium corporis callosi, posterior limb of internal capsule, hippocampus and fornix combined with measurement of Evans index is a promising MRI biomarker of NPH and could be used for NPH diagnostics and in the differential diagnosis from AD and other dementias.

Preventive effects of curcumin on the development of azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice.

PubMed

Kubota, Masaya; Shimizu, Masahito; Sakai, Hiroyasu; Yasuda, Yoichi; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

2012-01-01

Obesity-related metabolic abnormalities include a state of chronic inflammation and adipocytokine imbalance, which increase the risk of colon cancer. Curcumin, a component of turmeric, exerts both cancer preventive and antiinflammatory properties. Curcumin is also expected to have the ability to reverse obesity-related metabolic derangements. The present study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Feeding with a diet containing 0.2% and 2.0% curcumin caused a significant reduction in the total number of colonic premalignant lesions compared with basal diet-fed mice. The expression levels of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 (COX-2) mRNAs on the colonic mucosa of AOM-treated mice were significantly decreased by curcumin administration. Dietary feeding with curcumin markedly activated AMP-activated kinase, decreased the expression of COX-2 protein, and inhibited nuclear factor-κB activity on the colonic mucosa of AOM-treated mice. Curcumin also increased the serum levels of adiponectin while conversely decreasing the serum levels of leptin and the weights of fat. In conclusion, curcumin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model, at least in part, by attenuating chronic inflammation and improving adipocytokine imbalance. Curcumin may be useful in the chemoprevention of colorectal carcinogenesis in obese individuals.

Magnetic resonance and computed tomographic imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus.

PubMed Central

Sibbitt, W L; Sibbitt, R R; Griffey, R H; Eckel, C; Bankhurst, A D

1989-01-01

Magnetic resonance (MR) imaging and computed tomography (CT) are useful for the evaluation of central nervous system (CNS) lupus. This report describes the use of cranial MR and CT in 21 patients with systemic lupus erythematosus (SLE) with acute neuropsychiatric symptoms manifested by headache, seizures, focal neurological deficits, psychosis, or organic brain syndrome. Computed tomography was found to be insensitive and detected only diffuse atrophy (two cases), cerebral infarct (one case), and intracerebral haemorrhage (one case) in the 21 patients. Cranial MR images obtained with a General Electric 1.5 tesla Signa unit detected labile and fixed areas of increased proton intensity interpreted as focal oedema (eight cases), infarct (10 cases), haemorrhage (one), atrophy (seven), and acute sinusitis (two). Focal oedema was characterised by labile, high intensity lesions in the gray or white matter of the cerebellum, cerebrum, or brain stem, which completely resolved after aggressive corticosteroid treatment. Most high intensity reversible or fixed lesions evident on MR were not apparent on cranial CT images. In several patients sequential MR images were valuable in monitoring the efforts of treatment. Although histological confirmation of the high intensity brain lesions apparent on MR is desirable, prior necropsy studies suggest that pathological confirmation may be difficult owing to the paucity of recognisable brain lesions in patients with CNS lupus. It is concluded that for the evaluation of acute neuropsychiatric SLE MR is useful and provides more information than cranial CT. Images PMID:2619353

Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model

PubMed Central

Lee, Young Bok; Kim, Su Jin; Park, Sae Mi; Lee, Kyung Ho; Han, Hyung Jin; Yu, Dong Soo; Woo, So Youn; Yun, Seong Taek; Hamm, Se-Yeong; Kim, Hong Jig

2016-01-01

Background Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. Objective This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. Methods The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. Results Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4+ Foxp3+ regulatory T cells in thermomineral balneotherapy compared with distilled water bath. Conclusion Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis. PMID:27081266

Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model.

PubMed

Lee, Young Bok; Kim, Su Jin; Park, Sae Mi; Lee, Kyung Ho; Han, Hyung Jin; Yu, Dong Soo; Woo, So Youn; Yun, Seong Taek; Hamm, Se-Yeong; Kim, Hong Jig; Kim, Jin-Wou

2016-04-01

Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4(+) Foxp3(+) regulatory T cells in thermomineral balneotherapy compared with distilled water bath. Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.

Interactions between prefrontal cortex and cerebellum revealed by trace eyelid conditioning.

PubMed

Kalmbach, Brian E; Ohyama, Tatsuya; Kreider, Joy C; Riusech, Frank; Mauk, Michael D

2009-01-01

Eyelid conditioning has proven useful for analysis of learning and computation in the cerebellum. Two variants, delay and trace conditioning, differ only by the relative timing of the training stimuli. Despite the subtlety of this difference, trace eyelid conditioning is prevented by lesions of the cerebellum, hippocampus, or medial prefrontal cortex (mPFC), whereas delay eyelid conditioning is prevented by cerebellar lesions and is largely unaffected by forebrain lesions. Here we test whether these lesion results can be explained by two assertions: (1) Cerebellar learning requires temporal overlap between the mossy fiber inputs activated by the tone conditioned stimulus (CS) and the climbing fiber inputs activated by the reinforcing unconditioned stimulus (US), and therefore (2) trace conditioning requires activity that outlasts the presentation of the CS in a subset of mossy fibers separate from those activated directly by the CS. By use of electrical stimulation of mossy fibers as a CS, we show that cerebellar learning during trace eyelid conditioning requires an input that persists during the stimulus-free trace interval. By use of reversible inactivation experiments, we provide evidence that this input arises from the mPFC and arrives at the cerebellum via a previously unidentified site in the pontine nuclei. In light of previous PFC recordings in various species, we suggest that trace eyelid conditioning involves an interaction between the persistent activity of delay cells in mPFC-a putative mechanism of working memory-and motor learning in the cerebellum.

Guided fluorescence diagnosis of childhood caries: preliminary measures correlate with depth of carious decay

NASA Astrophysics Data System (ADS)

Timoshchuk, Mari-Alina; Zhang, Liang; Dickinson, Brian A.; Ridge, Jeremy S.; Kim, Amy S.; Baltuck, Camille T.; Nelson, Leonard Y.; Berg, Joel H.; Seibel, Eric J.

2014-02-01

The current rise in childhood caries worldwide has increased the demand for portable technologies that can quickly and accurately detect and diagnose early stage carious lesions. These lesions, if identified at an early stage, can be reversed with remineralization treatments, education, and improvements in home care. A multi-modal optical prototype for detecting and diagnosing occlusal caries demineralization in vivo has been developed and pilot tested. The device uses a 405-nm laser as a scanned illumination source to obtain high resolution and high surface contrast reflectance images, which allows the user to quickly image and screen for any signs of demineralized enamel. When a suspicious region is located, the device can be switched to perform dual laser fluorescence spectroscopy using 405-nm and 532-nm laser excitations. These spectra are used to compute an auto-fluorescence (AF) ratio of the suspicious region and the percent difference of AF ratios from a healthy region of the same tooth. The device was tested on 7 children's teeth in vivo with clinically diagnosed carious lesions. Lesion depth was then visually estimated from the video image using the 405-nm scanned light source, and within a month the maximum drill depth was assessed by a clinician. The researcher and clinicians were masked from previous measurements in a blinded study protocol. Preliminary results show that the ratiometric percent difference measurement of the AF spectrum of the tooth correlates with the severity of the demineralization as assessed by the clinician after drilling.

Gastroprotective effects of flavonoids in plant extracts.

PubMed

Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Konturek, P C; Brzozowski, T; Ghegotsky, M R

2005-03-01

The purpose of this paper is to overview the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulcer activities. In addition, we assessed whether these compounds are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically (i.g.). The following plant-originated flavonoid substances were considered; Solon (Sophoradin extract), Amaranth seed extract, grapefruit-seed extract (GSE) and capsaicin (extract of chilly pepper). The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). Male Wistar rats, weighing 180-220 g fasted for 24 h before the study where used 100% ethanol was applied i.g. to induce gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment with L-NNA. We conclude that plant-originated flavonoid substances are highly gastroprotective probably due to enhancement of the expression of constitutive NOS and release of NO and neuropeptides such as calcitonin gene related peptide (CGRP) released from sensory afferent nerves increasing gastric microcirculation.

Influence of plant-originated gastroproteciive and antiulcer substances on gastric mucosal repair.

PubMed

Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Brzozowski, T; Gzhegotsky, M R

2004-01-01

Fundamental basis of cellular and molecular mechanisms involved in mucosal injury and repair in gastrointestinal tract helps to develop new therapeutic approaches to various gut mucosal injury- related diseases. The study was aimed to assess the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulceric activities and to deteminate if these effects are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically. The following plant-originated substances were considered: Solon, capsaicin, grapefruit-seed extract and amaranth. The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). male Wistar rats, weighing 180-220 g fasted for 24 h before the study, 100% ethanol was applied ig to induced gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by an increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment-with L-NNA. Plant-originated substances are highly gastroprotective probably due to enhancement of the expression of NOS I, NO release and an increase in gastric microcirculation.

Antigen tissue distribution of Avian bornavirus (ABV) in psittacine birds with natural spontaneous proventricular dilatation disease and ABV genotype 1 infection.

PubMed

Wünschmann, Arno; Honkavuori, Kirsi; Briese, Thomas; Lipkin, W Ian; Shivers, Jan; Armien, Aníbal G

2011-07-01

Tissues of 10 psittacines from aviary 1 ("case birds") and 5 psittacines from different aviaries were investigated for the presence of Avian bornavirus (ABV) antigen by immunohistochemistry using a polyclonal serum specific for the viral nucleocapsid (N) protein. Seven of 10 case birds had clinical signs, and necropsy findings consistent with proventricular dilatation disease (PDD) while 3 case birds and the 5 birds from other aviaries did not exhibit signs and lesions of this disease. In birds with clinical signs of PDD, ABV antigen was largely limited to neuroectodermal cells including neurons, astroglia, and ependymal cells of the central nervous system, neurons of the peripheral nervous system, and adrenal cells. ABV antigen was present in the nuclei and cytoplasm of infected cells. In 2 case birds that lacked signs and lesions of PDD, viral antigen had a more widespread distribution and was present in nuclei and cytoplasm of epithelial cells of the alimentary and urogenital tract, retina, heart, skeletal muscle, and skin in addition to the mentioned neuroectodermal cells. ABV RNA was identified by reverse transcription polymerase chain reaction (RT-PCR) in tissues of all 7 case birds available for testing from aviary 1, including 4 birds with PDD lesions and the 3 birds without PDD lesions. Sequencing and phylogenetic analysis indicated the presence of ABV genotype 1 in all cases. Findings further substantiate a role of ABV in PDD of psittacine bird species.

Antigen tissue distribution of Avian bornavirus (ABV) in psittacine birds with natural spontaneous proventricular dilatation disease and ABV genotype 1 infection

PubMed Central

Wünschmann, Arno; Honkavuori, Kirsi; Briese, Thomas; Lipkin, W. Ian; Shivers, Jan; Armien, Aníbal G.

2014-01-01

Tissues of 10 psittacines from aviary 1 (“case birds”) and 5 psittacines from different aviaries were investigated for the presence of Avian bornavirus (ABV) antigen by immunohistochemistry using a polyclonal serum specific for the viral nucleocapsid (N) protein. Seven of 10 case birds had clinical signs, and necropsy findings consistent with proventricular dilatation disease (PDD) while 3 case birds and the 5 birds from other aviaries did not exhibit signs and lesions of this disease. In birds with clinical signs of PDD, ABV antigen was largely limited to neuroectodermal cells including neurons, astroglia, and ependymal cells of the central nervous system, neurons of the peripheral nervous system, and adrenal cells. ABV antigen was present in the nuclei and cytoplasm of infected cells. In 2 case birds that lacked signs and lesions of PDD, viral antigen had a more widespread distribution and was present in nuclei and cytoplasm of epithelial cells of the alimentary and urogenital tract, retina, heart, skeletal muscle, and skin in addition to the mentioned neuroectodermal cells. ABV RNA was identified by reverse transcription polymerase chain reaction (RT-PCR) in tissues of all 7 case birds available for testing from aviary 1, including 4 birds with PDD lesions and the 3 birds without PDD lesions. Sequencing and phylogenetic analysis indicated the presence of ABV genotype 1 in all cases. Findings further substantiate a role of ABV in PDD of psittacine bird species. PMID:21908314

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: Development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

NASA Astrophysics Data System (ADS)

Peng, Yu-Hao; Heintz, Ryan; Wang, Zhuo; Guo, Yumei; Myers, Kalisa; Scremin, Oscar; Maarek, Jean-Michel; Holschneider, Daniel

2014-12-01

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex--changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies.

SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honig, N; Alani, S; Schlocker, A

Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam deliverymore » efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer monitor units, and quicker delivery time.« less

Correlation of simultaneously acquired diffusion-weighted imaging and 2-deoxy-[18F] fluoro-2-D-glucose positron emission tomography of pulmonary lesions in a dedicated whole-body magnetic resonance/positron emission tomography system.

PubMed

Schmidt, Holger; Brendle, Cornelia; Schraml, Christina; Martirosian, Petros; Bezrukov, Ilja; Hetzel, Jürgen; Müller, Mark; Sauter, Alexander; Claussen, Claus D; Pfannenberg, Christina; Schwenzer, Nina F

2013-05-01

Hybrid whole-body magnetic resonance/positron emission tomography (MR/PET) systems are a new diagnostic tool enabling the simultaneous acquisition of morphologic and multiple functional data and thus allowing for a diversified characterization of oncological diseases.The aim of this study was to investigate the image and alignment quality of MR/PET in patients with pulmonary lesions and to compare the congruency of the 2 functional measurements of diffusion-weighted imaging (DWI) in MR imaging and 2-deoxy-[18F] fluoro-2-D-glucose (FDG) uptake in PET. A total of 15 patients were examined with a routine positron emission tomography/computer tomography (PET/CT) protocol and, subsequently, in a whole-body MR/PET scanner allowing for simultaneous PET and MR data acquisition. The PET and MR image quality was assessed visually using a 4-point score (1, insufficient; 4, excellent). The alignment quality of the rigidly registered PET/CT and MR/PET data sets was investigated on the basis of multiple anatomic landmarks of the lung using a scoring system from 1 (no alignment) to 4 (very good alignment). In addition, the alignment quality of the tumor lesions in PET/CT and MR/PET as well as for retrospective fusion of PET from PET/CT and MR images was assessed quantitatively and was compared between lesions strongly or less influenced by respiratory motion. The correlation of the simultaneously acquired DWI and FDG uptake in the pulmonary masses was analyzed using the minimum and mean apparent diffusion coefficient (ADC min and ADC mean) as well as the maximum and mean standardized uptake value (SUV max and SUV mean), respectively. In addition, the correlation of SUV max from PET/CT data was investigated as well. On lesions 3 cm or greater, a voxelwise analysis of ADC and SUV was performed. The visual evaluation revealed excellent image quality of the PET images (mean [SD] score, 3.6 [0.5]) and overall good image quality of DWI (mean [SD] score of 2.5 [0.5] for ADC maps and 2.7 [0.5] for diffusion-weighted images, respectively). The alignment quality of the data sets was very good in both MR/PET and PET/CT without significant differences (overall mean [SD] score of MR/PET, 3.8 [0.4]; PET/CT 3.6 [0.5]). Also, the alignment quality of the tumor lesions showed no significant differences between PET/CT and MR/PET (mean cumulative misalignment of MR/PET, 7.7 mm; PET/CT, 7.0 mm; P = 0.705) but between both modalities and a retrospective fusion (mean cumulative misalignment, 17.1 mm; P = 0.002 and P = 0.008 for PET/CT and MR/PET, respectively). Also, the comparison of the lesions strongly or less influenced by respiratory motion showed significant differences only for the retrospective fusion (21.3 mm vs 11.5 mm, respectively; P = 0.043). The ADC min and SUV max as measures of the cell density and glucose metabolism showed a significant reverse correlation (r = -0.80; P = 0.0006). No significant correlation was found between ADC mean and SUV mean (r = -0.42; P = 0.1392). Also, SUV max from the PET/CT data showed significant reverse correlation to ADC min (r = -0.62; P = 0.019). The voxelwise analysis of 5 pulmonary lesions each showed weak but significant negative correlation between ADC and SUV. Examinations of pulmonary lesions in a simultaneous whole-body MR/PET system provide diagnostic image quality in both modalities. Although DWI and FDG-PET reflect different tissue properties, there may very well be an association between the measures of both methods most probably because of increased cellularity and glucose metabolism of FDG-avid pulmonary lesions. A voxelwise DWI and FDG-PET correlation might provide a more sophisticated spatial characterization of pulmonary lesions.

Thalamic Control of Dorsomedial Striatum Regulates Internal State to Guide Goal-Directed Action Selection.

PubMed

Bradfield, Laura A; Balleine, Bernard W

2017-03-29

We (Bradfield et al., 2013) have demonstrated previously that parafascicular thalamic nucleus (PF)-controlled neurons in the posterior dorsomedial striatum (pDMS) are critical for interlacing new and existing action-outcome contingencies to control goal-directed action. Based on these findings, it was suggested that animals with a dysfunctional PF-pDMS pathway might suffer a deficit in creating or retrieving internal contexts or "states" on which such information could become conditional. To assess this hypothesis more directly, rats were given a disconnection treatment using contralateral cytotoxic lesions of the PF and pDMS (Group CONTRA) or ipsilateral control lesions (Group IPSI) and trained to press a right and left lever for sucrose and pellet outcomes, after which these contingencies were reversed. The rats were then given an outcome devaluation test (all experiments) and a test of outcome-specific reinstatement (Experiments 1 and 3). We found that devaluation performance was intact for both groups after training of initial contingencies, but impaired for Group CONTRA after reversal. However, performance was restored by additional reversal training. Furthermore, when tested a second time after reversal training, rats in both groups demonstrated responding in accordance with the original contingencies, providing direct evidence of modulation of action selection by state. Finally, we found that external context could substitute for internal state and so could rescue responding in Group CONTRA, but only in the reinstatement test. Together, these findings suggest that animals use internal state information to guide action selection and that this information is modulated by the PF-pDMS pathway. SIGNIFICANCE STATEMENT Individuals with Parkinson's disease dementia often suffer a characteristic deficit in "cognitive flexibility." It has been suggested that neurodegeneration in the pathway between the centromedian/parafascicular thalalmic nucleus (PF) and striatum might underlie such deficits (Smith et al., 2014). In rats, we have similarly observed that a functional disconnection of the PF-posterior dorsomedial striatal pathway produces a specific impairment in the ability to alter goal-directed actions (Bradfield et al., 2013). It was suggested that this impairment could be a result of a deficit in state modulation. Here, we present four experiments that provide evidence for this hypothesis and suggest several ways (e.g., extended practice, providing external cues) in which this state modulation can be rescued. Copyright © 2017 the authors 0270-6474/17/373721-13$15.00/0.

Reversible Disruption of Neuronal Mitochondria by Ischemic and Traumatic Injury Revealed by Quantitative Two-Photon Imaging in the Neocortex of Anesthetized Mice

PubMed Central

Kislin, Mikhail; Sword, Jeremy; Fomitcheva, Ioulia V.; Croom, Deborah; Pryazhnikov, Evgeny; Lihavainen, Eero; Toptunov, Dmytro; Rauvala, Heikki; Ribeiro, Andre S.

2017-01-01

Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1–2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries. SIGNIFICANCE STATEMENT During ischemic stroke or brain trauma, mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca2+, or kill neurons by releasing proapoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate, and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions. PMID:28077713

Clinical image: MRI during migraine with aura

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNeal, A.C.

1996-03-01

Migraine refers to severe headaches that are usually unilateral, throbbing, and associated with nausea, vomiting, photophobia, and phonophobia. Migraine with aura (formerly called {open_quotes}classic migraine{close_quotes}) consists of the headache preceded or accompanied by neurological dysfunction. This dysfunction (aura) usually involves visual and sensory symptoms. The patient described herein experienced migraine with aura. MRI during and after the attack showed a reversible abnormality of the right posterior cerebral artery, with no parenchymal lesions. This appears to be the first report of abnormal MR vascular imaging during migraine with aura. 10 refs., 2 figs.

Saphenous Vein Graft Perforation During Percutaneous Coronary Intervention - A Nightmare to be Avoided.

PubMed

Deora, Surender; Shah, Sanjay C; Patel, Tejas M

2015-01-01

Percutaneous coronary interventions (PCIs) of saphenous vein grafts (SVGs) is challenging and is associated with adverse short- and long-term clinical outcome as compared to native coronary arteries. SVG perforation is rare but catastrophic and needs immediate attention. Various factors predisposing for SVG perforation are old degenerated graft, ulcerated plaque, severe fibrotic, or calcified lesion necessitating high pressure balloon or stent inflation, use of intravascular ultrasound (IVUS) or other atheroablative devices. Management includes prolonged balloon occlusion, reversal of anticoagulation, use of covered stent, and emergency pericadiocentesis if required.

Urinary retention associated with herpes zoster infection.

PubMed

Cohen, L M; Fowler, J F; Owen, L G; Callen, J P

1993-01-01

Herpes zoster infection particularly involving the sacral dermatomes has been associated with bladder and bowel dysfunction, most commonly urinary retention. We report two patients who developed acute urinary retention, one of whom also had constipation, within days of herpes zoster skin lesions of the S2-S4 dermatomes. Herpes zoster is a reversible cause of neurogenic bladder and bowel dysfunction and should be considered in a patient that presents with acute urinary retention and/or constipation. Sensory abnormalities and flaccid detrusor paralysis are most likely involved in the pathogenesis.

Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways.

PubMed

Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

2005-11-07

Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.

Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

PubMed Central

Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

2005-01-01

AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS: We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. RESULTS: Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 μg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION: GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves. PMID:16425415

Pathology of ocular lesions associated with gas supersaturation in white seabass.

PubMed

Smiley, Jeffrey E; Okihiro, Mark S; Drawbridge, Mark A; Kaufmann, Ronald S

2012-03-01

Cultured juvenile white seabass Atractoscion nobilis (WSB) can suffer from intraocular emphysemas and exophthalmia in the hatchery environment. To identify the cause, two size-groups of WSB were exposed to five gas saturation levels, ranging from 98% to 122% total gas pressure (TGP), over a 96-h exposure period in 18 degrees C and 23 degrees C seawater. Histological examination revealed that the gross and subgross lesions associated with gas supersaturation included corneal and orbital emphysema, along with subretinal, optic nerve, and iridial hemorrhage. Corneal emphysema was the most prominent gross lesion, with the severity and prevalence increasing between size-groups and water temperatures as TGP increased. Following the same pattern was orbital emphysema, which affected more than 93% of the fish examined and caused hemorrhage in the subretinal space, around the optic nerve, in the iris, or a combination thereof. Iridial hemorrhage occurred in 91% of the fish examined and decreased significantly with fish size. The prevalence and severity of hemorrhage in the subretinal space increased significantly with TGP and fish size but not with temperature. Optic nerve hemorrhage was absent in small fish exposed at 18 degrees C but increased significantly with temperature and fish size. The reverse was true for the large fish.

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

PubMed Central

Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

2017-01-01

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke. PMID:28706475

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

PubMed

Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

2017-01-01

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem.

PubMed

Martins-Júnior, J L; Bernardi, M M; Bondan, E F

2016-03-01

Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test. Copyright © 2016 Elsevier Inc. All rights reserved.

Midline thalamic reuniens lesions improve executive behaviors.

PubMed

Prasad, J A; Abela, A R; Chudasama, Y

2017-03-14

The role of the thalamus in complex cognitive behavior is a topic of increasing interest. Here we demonstrate that lesions of the nucleus reuniens (NRe), a midline thalamic nucleus interconnected with both hippocampal and prefrontal circuitry, lead to enhancement of executive behaviors typically associated with the prefrontal cortex. Rats were tested on four behavioral tasks: (1) the combined attention-memory (CAM) task, which simultaneously assessed attention to a visual target and memory for that target over a variable delay; (2) spatial memory using a radial arm maze, (3) discrimination and reversal learning using a touchscreen operant platform, and (4) decision-making with delayed outcomes. Following NRe lesions, the animals became more efficient in their performance, responding with shorter reaction times but also less impulsively than controls. This change, combined with a decrease in perseverative responses, led to focused attention in the CAM task and accelerated learning in the visual discrimination task. There were no observed changes in tasks involving either spatial memory or value-based decision making. These data complement ongoing efforts to understand the role of midline thalamic structures in human cognition, including the development of thalamic stimulation as a therapeutic strategy for acquired cognitive disabilities (Schiff, 2008; Mair et al., 2011), and point to the NRe as a potential target for clinical intervention. Published by Elsevier Ltd.

Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician

PubMed Central

Shah, Dhwani B.; Pesiridou, Angeliki; Baltuch, Gordon H.; Malone, Donald A.; O’Reardon, John P.

2008-01-01

Over the past 20 years, there has been a concerted effort to expand our understanding of the neural circuitry involved in the pathogenesis of psychiatric disorders. Distinct neuronal circuits and networks have been implicated in obsessive compulsive disorder (OCD) and major depressive disorder (MDD) involving feedback loops between the cortex, striatum, and thalamus. When neurosurgery is used as a therapeutic tool in severe OCD and MDD, the goal is to modulate specific targets or nodes within these networks in an effort to produce symptom relief. Currently, four lesioning neurosurgical procedures are utilized for treatment refractory OCD and MDD: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Deep brain stimulation (DBS) is a novel neurosurgical approach that has some distinct advantages over lesioning procedures. With DBS, the desired clinical effect can be achieved by reversible, high frequency stimulation in a nucleus or at a node in the circuit without the need to produce an irreversible lesion. Recent trials of deep brain stimulation in both OCD and MDD at several neuroanatomical targets have reported promising early results in highly refractory patients and with a good safety profile. Future definitive trials in MDD and OCD are envisaged. PMID:19727257

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma.

PubMed

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W; Novane, Nora; Shah, Jatin J; Davis, Richard E; Hou, Jian; Gagel, Robert F; Yang, Jing

2016-08-24

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. Copyright © 2016, American Association for the Advancement of Science.

Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning

PubMed Central

Regnier-Golanov, Angelique S.; Britz, Gavin W.

2017-01-01

Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO) global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1) hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS)-injected) animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”. PMID:28934119

Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs.

PubMed

Qeska, V; Barthel, Y; Iseringhausen, M; Tipold, A; Stein, V M; Khan, M A; Baumgärtner, W; Beineke, A

2013-12-15

Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis. © 2013 Elsevier B.V. All rights reserved.

Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation.

PubMed

Etiévant, A; Oosterhof, C; Bétry, C; Abrial, E; Novo-Perez, M; Rovera, R; Scarna, H; Devader, C; Mazella, J; Wegener, G; Sánchez, C; Dkhissi-Benyahya, O; Gronfier, C; Coizet, V; Beaulieu, J M; Blier, P; Lucas, G; Haddjeri, N

2015-08-01

Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

How atypical is atypical language dominance?

PubMed

Knecht, S; Jansen, A; Frank, A; van Randenborgh, J; Sommer, J; Kanowski, M; Heinze, H J

2003-04-01

Atypical, right-hemisphere language dominance is poorly understood. It is often observed in patients with brain reorganization due to lesions early in life. It can also be encountered in seemingly normal individuals. We compared the patterns of neural language activation in 7 individuals with left- and 7 with right-hemisphere language dominance, none of whom had any evidence of brain lesions. We speculated that incongruencies in the activation patterns in atypical, right-hemisphere language dominance could indicate a reorganized neural language system after undetected early brain damage. Functional magnetic resonance imaging analysis of brain activation during phonetic word generation demonstrated (1). no increased activation in the subdominant hemisphere in right compared to left language dominance, (2). a similar variability in the pattern of activation in both groups, and (3). a mirror reverse pattern of activation in right- compared to left-hemisphere dominant subjects. These findings support the view that in individuals with an unrevealing medical history right-hemispheric dominance constitutes a natural rather than an abortive variant of language lateralization.

Crossed Wernicke's aphasia: a case report.

PubMed

Sheehy, Laurie M; Haines, Mary E

2004-04-01

Crossed aphasia is a phenomenon in which an individual sustains a lesion in the right hemisphere (typically non-language dominant), but who exhibits an aphasic syndrome. The authors present a case study of an individual with crossed aphasia (CA) in an attempt to provide anecdotal information for four questions posed by : (a). Is CA a reversal of the normal cerebral hemisphere pattern of language function? (b). Does the presence of aphasia following a right cerebral hemisphere lesion indicate that typical right hemisphere functions (e.g., visual perception) are intact? (c). How may the aphasia's presentation differ from typical left hemisphere aphasias? And (d). is the pattern of improvement following CA similar to that of typical left hemisphere aphasias? We longitudinally examined the communicative-cognitive performance of an adult man with crossed aphasia of the Wernicke's type following a cerebrovascular accident. A 21-week follow-up evaluation indicated improvements in his language functioning from our initial evaluation, but he continued to exhibit a classic, moderately severe Wernicke's aphasia.

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects*

PubMed Central

Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros

2014-01-01

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656

Progressive Multifocal Leukoencephalopathy Complicating HIV-1 Infection

PubMed Central

Cinque, Paola; Koralnik, Igor J.; Gerevini, Simonetta; Miro, Jose M.; Price, Richard W.

2010-01-01

Progressive multifocal leukoencephalopathy (PML) caused by the polyomavirus, JC virus (JCV), is one of the most dreaded complications of HIV-1 infection. Unlike other opportunistic infections, PML may present while blood CD4+ T cells remain above AIDS-defining levels and while patients receive combined antiretroviral therapy (cART), either shortly after starting or, more rarely, during chronic successful treatment. PML can be suspected by typical presentation with focal neurological deficits and corresponding demyelinating lesions at magnetic resonance imaging (MRI), while definitive diagnosis requires identification of JCV in cerebrospinal fluid (CSF) or brain tissue. While there is no specific treatment, reversal of immunosuppression by cART leads to clinical and MRI stabilization in 50-60% of PML patients and JCV clearance from CSF. A proportion of cART-treated patients develop inflammatory lesions, which may either accompany a favorable outcome or associate with clinical worsening. The reasons for variability in PML natural history and treatment responses are largely undefined, and more specific and rational approaches to management are sorely needed. PMID:19778765

Acute toxicity by water containing hexavalent or trivalent chromium in native Brazilian fish, Piaractus mesopotamicus: anatomopathological alterations and mortality.

PubMed

Castro, Marcello Pardi; de Moraes, Flávio Ruas; Fujimoto, Rodrigo Yudi; da Cruz, Claudinei; Belo, Marco Antonio de Andrade; de Moraes, Julieta Rodini Engrácia

2014-02-01

This study evaluated the toxicity of hexavalent and trivalent compounds of chromium to the pacu, Piaractus mesopotamicus, in acute exposures of 96 h through mortality and histopathological responses. Hexavalent potassium dichromate was more toxic than trivalent compounds of chromium chloride, chromium oxide and chromium carbochelate. Sufficient mortalities occurred only with potassium dichromate to yield an LC50 value at 124.2 mg L(-1). Hexavalent chromium caused reversible and irreversible lesions, which may affect organ functionality. Histopathological evaluation showed that trivalent chromium caused lesions of lower severity. Pacu subjected to different concentrations of chromium carbochelate showed no histopathological changes in the kidneys, liver, skin and gills, being similar to those of the control fish. Among the three sources of Cr(3+), only chromium chloride at 200 mg L(-1) resulted in mortality, which reached 100 % within the first 18 h. These findings confirm that trivalent chromium, when administered within recommended levels, may be used safely in aquaculture.

Sugar Alcohols, Caries Incidence, and Remineralization of Caries Lesions: A Literature Review

PubMed Central

Mäkinen, Kauko K.

2010-01-01

Remineralization of minor enamel defects is a normal physiological process that is well known to clinicians and researchers in dentistry and oral biology. This process can be facilitated by various dietary and oral hygiene procedures and may also concern dentin caries lesions. Dental caries is reversible if detected and treated sufficiently early. Habitual use of xylitol, a sugar alcohol of the pentitol type, can be associated with significant reduction in caries incidence and with tooth remineralization. Other dietary polyols that can remarkably lower the incidence of caries include erythritol which is a tetritol-type alditol. Based on known molecular parameters of simple dietary alditols, it is conceivable to predict that their efficacy in caries prevention will follow the homologous series, that is, that the number of OH-groups present in the alditol molecule will determine the efficacy as follows: erythritol ≥ xylitol > sorbitol. The possible difference between erythritol and xylitol must be confirmed in future clinical trials. PMID:20339492

[Human papillomavirus in the pubic hair follicles of men and cervical lesions in their female sexual partners].

PubMed

Han, Tao; Sun, Xuan; Wang, You-Bao; Zhu, Chang-Ming; Xu, Xiang-Qian

2013-09-01

To investigate the association of human papillomavirus (HPV) in the pubic hair follicles of males with HPV infection in their female sexual partners. We included in this study 21 female patients with HPV infection, including 8 cases of cervical cancer, 5 cases of atypical cervical hyperplasia, 5 cases of cervical condyloma, and 3 cases with unidentified causes. We also enlisted 52 men without visible condyloma acuminatum in the external genitalia as healthy controls. We detected HPV in the pubic hair follicles of the female patients' male sexual partners and the healthy male controls by PCR and reverse hybridization in situ. HPV positive was found in 6 (28.6%) of the 21 women's male partners, in whom the HPV types were correspondent situ. to those of the female patients. HPV in the pubic hair follicles of men might be one of the causes of HPV-related cervical lesions in their female sexual partners.

[The neuroscientific work of Justo Gonzalo (1910-1986): the center syndrome and reversal metamorphopsia].

PubMed

Arias, M; Gonzalo, I

2004-10-01

The Spanish neuroscientist Justo Gonzalo Rodriguez-Leal (Barcelona 1910, Madrid 1986) carried out different studies on cerebral functions, highlighting those made in patients with encephalic injuries suffered during the Spanish civil war. His book "Investigaciones sobre la nueva dinámica cerebral. La actividad cerebral en función de las condiciones de excitabilidad nerviosa", published in two volumes (the first one in 1945 and the second one five years later), gathers some of his fundamental contributions, among which the so-called central syndrome stands out. A dominant parietal lesion (central) equidistant from the visual, sensorial and auditory projection areas can lead to diverse perceptive dysfunctions, among them inversions in visual, tactile and acoustic perception. As the lesion becomes more peripheral, the resulting defect will be more unisensorial and crossed, while when it approaches the central region, the disorders will be bilateral and polysensorial. Justo Gonzalo explained all these phenomena later by a gradient system.

Pulmonary preinvasive neoplasia.

PubMed

Kerr, K M

2001-04-01

Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology. Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment.

Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005.

PubMed

Higgins, Michael A; Rossmeisl, John H; Panciera, David L

2006-01-01

With the exception of myxedema coma, central nervous system signs are rare in hypothyroid dogs. Central vestibular dysfunction is a possible and reversible manifestation of hypothyroidism. Medical records of dogs with vestibular dysfunction and hypothyroidism were reviewed. Of 113 records identified, 10 dogs with at least 2 concurrent clinical neurologic abnormalities localizable to the central vestibular system were included. Retrospective, descriptive study. Median age at diagnosis was 7 years (range, 5-10 years). All dogs were referred for progressive neurologic disease. Lesions were localized to the myelencephalic region in 5 dogs and to the vestibulocerebellum in 5 dogs. Two dogs had evidence of multifocal intracranial disease. Non-neurologic physical abnormalities suggestive of hypothyroidism were absent in 7 of 10 dogs. Hypercholesterolemia was the only consistent clinicopathologic abnormality detected, and was present in 7 of 10 dogs. All dogs had total thyroxine (TT4) and free thyroxine (fT4) concentrations below reference ranges, and 9 of 10 had increased TSH concentrations. Intracranial imaging studies were normal in 5 of 8 dogs, and identified lesions consistent with infarctions in 3 of 8 dogs. Albuminocytologic dissociation was detected in 5 of 6 CSF analyses. Brainstem auditory-evoked responses disclosed prolonged wave V latencies in 3 of 4 dogs tested. No other causes of central vestibular dysfunction were identified during other diagnostic investigations. The median time from initiation of treatment to clinical improvement was 4 days. Vestibular signs resolved in 9 of 10 dogs within 4 weeks. Although the pathogenesis in dogs without evidence of infarction is unknown, central vestibular dysfunction appears to be a rare but reversible neurologic sequelae of hypothyroidism.

Kainate and metabolic perturbation mimicking spinal injury differentially contribute to early damage of locomotor networks in the in vitro neonatal rat spinal cord.

PubMed

Taccola, G; Margaryan, G; Mladinic, M; Nistri, A

2008-08-13

Acute spinal cord injury evolves rapidly to produce secondary damage even to initially spared areas. The result is loss of locomotion, rarely reversible in man. It is, therefore, important to understand the early pathophysiological processes which affect spinal locomotor networks. Regardless of their etiology, spinal lesions are believed to include combinatorial effects of excitotoxicity and severe stroke-like metabolic perturbations. To clarify the relative contribution by excitotoxicity and toxic metabolites to dysfunction of locomotor networks, spinal reflexes and intrinsic network rhythmicity, we used, as a model, the in vitro thoraco-lumbar spinal cord of the neonatal rat treated (1 h) with either kainate or a pathological medium (containing free radicals and hypoxic/aglycemic conditions), or their combination. After washout, electrophysiological responses were monitored for 24 h and cell damage analyzed histologically. Kainate suppressed fictive locomotion irreversibly, while it reversibly blocked neuronal excitability and intrinsic bursting induced by synaptic inhibition block. This result was associated with significant neuronal loss around the central canal. Combining kainate with the pathological medium evoked extensive, irreversible damage to the spinal cord. The pathological medium alone slowed down fictive locomotion and intrinsic bursting: these oscillatory patterns remained throughout without regaining their control properties. This phenomenon was associated with polysynaptic reflex depression and preferential damage to glial cells, while neurons were comparatively spared. Our model suggests distinct roles of excitotoxicity and metabolic dysfunction in the acute damage of locomotor networks, indicating that different strategies might be necessary to treat the various early components of acute spinal cord lesion.

The secret trumps, impelling the pathogenicity of tubercle bacilli.

PubMed

Cardona, Pere-Joan; Ivanyi, Juraj

2011-03-01

Confrontation between invading microbial pathogens and host defense systems involves intricate cellular and molecular interactions. Here we discuss the virulence factors as trumps, overriding the contest in favor of the tubercle bacillus (Mycobacterium tuberculosis). It evolved a number of molecular constituents, which can interfere with antigen presentation and Toll receptor function, thus impairing immune defenses. It also evolved stress responses, which can drive its cell cycle into a non-replicating, low metabolic mode. Although the low counts of latent bacilli prevent their direct detection, we contend that they retain a capacity to survive for long periods in foamy macrophages and within the necrotic parts of lung granulomas. We attributed significance to drainage of M. tuberculosis by the alveolar fluid: while out-flow is responsible for the clearance, the reverse-flow has an important capacity to re-infect the lungs and to transmit the infection to new recipients. We consider the cycling between replicating and latent organisms to be a continuous process, which is a departure from the concept of long-lived dormant organisms, with a capacity to resuscitate. These aspects impinge also on the actions of isoniazid (INH) chemotherapy and on the topography of human lung lesions. Eventually, fibrosis of the connective tissue of the lungs is known to encapsulate lung lesions, thus limiting the impact of both outward and reverse drainage. In conclusion, the novelty of our views on M. tuberculosis-host interactions rests in the dynamic perception of M. tuberculosis latency and its evolutionary importance for the pathogenesis of tuberculosis. Copyright © 2011 Elsevier España S.L. All rights reserved.

Fluoride toothpaste containing 1.5% arginine and insoluble calcium as a new standard of care in caries prevention.

PubMed

ten Cate, J M; Cummins, D

2013-01-01

In spite of obvious achievements in prevention, caries remains a prevalent disease. Fluorides are effective by inhibiting enamel and dentin demineralization and enhancing remineralization, but have little or no influence on bacterial processes in dental plaque. Dental caries is a continuum of stages from reversible, early lesions to irreversible, pre-cavitated lesions and, ultimately, to cavities. Prevention should focus on strengthening protective and reducing pathological factors, and careful monitoring of the disease state. While fluoride and the mineral aspects of caries have been in focus for decades, new insights into the etiology of caries have generated novel concepts and approaches to its prevention and treatment. The observation that some plaque bacteria can produce alkali metabolites and, thus, raise pH or neutralize acid formed in plaque has long been known. Such pH rise factors are related to caries susceptibility. Nourishing the plaque with substrates that encourage alkali-producing reactions is a protective factor in the caries continuum. This article reviews the results of clinical studies with a novel toothpaste containing 1.5% arginine, an insoluble calcium compound, and fluoride which have demonstrated superior remineralization of white spot enamel lesions and rehardening of root surface lesions, favorable effects on the de-/remineralization balance, as well as superior cavity prevention efficacy compared to toothpaste with fluoride alone. Studies have also confirmed formation of ammonia and elevated pH levels in subjects using the arginine-containing toothpaste. This novel toothpaste effectively combines the established effects of fluoride on de- and remineralization with reduction of caries-inducing pathological factors resulting from plaque metabolism.

Intravascular lymphoma: magnetic resonance imaging correlates of disease dynamics within the central nervous system

PubMed Central

Baehring, J; Henchcliffe, C; Ledezma, C; Fulbright, R; Hochberg, F

2005-01-01

Background: Intravascular lymphoma (IVL) is a rare non-Hodgkin's lymphoma with relative predilection for the central nervous system. In the absence of extraneural manifestations, the disease is not recognised until autopsy in the majority of cases underlining the need for new clinical markers. Methods: This is a retrospective series of five patients with IVL seen at a single institution over three years. An advanced magnetic resonance imaging (MRI) protocol was performed at various time points prior to diagnosis and during treatment. Results: MRI revealed multiple lesions scattered throughout the cerebral hemispheres; the brainstem, cerebellum, and spinal cord were less frequently involved. On initial presentation, hyperintense lesions were seen on diffusion weighted images suggestive of ischaemia in three of four patients in whom the images were obtained at that time point. In four patients lesions were also identifiable as hyperintense areas on fluid attenuated inversion recovery (FLAIR) sequences. Initial contrast enhancement was encountered in three cases. Diffusion weighted imaging lesions either vanished or followed the typical pattern of an ischaemic small vessel stroke with evolution of abnormal FLAIR signal followed by enhancement with gadolinium in the subacute stage and tissue loss in the chronic stage. Diffusion weighted imaging and FLAIR abnormalities proved to be partially reversible, correlating with the response to chemotherapy. Conclusion: We provide the first detailed description of the dynamic pattern of diffusion weighted MRI in IVL. These patterns in combination with systemic findings may facilitate early diagnosis and serve as a new tool to monitor treatment response. PMID:15774442

Vulnerability of the Medial Frontal Corticospinal Projection Accompanies Combined Lateral Frontal and Parietal Cortex Injury in Rhesus Monkey

PubMed Central

Morecraft, R.J.; Ge, J.; Stilwell-Morecraft, K.S.; McNeal, D.W.; Hynes, S.M.; Pizzimenti, M.A.; Rotella, D.L.; Darling, W.G.

2014-01-01

Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction leading to upper extremity paresis, paresthesia and sensory loss. Motor recovery is often poor and the mechanisms that support, or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1. Isolated injury to the frontoparietal arm/hand region resulted in a significant loss of contralateral corticospinal boutons from M2 compared to controls. Specifically, reductions occurred in the medial and lateral parts of lamina VII and the dorsal quadrants of lamina IX. There were no statistical differences in the ipsilateral corticospinal projection. Contrary to isolated lateral frontal motor injury (F2 lesion) which results in substantial increases in contralateral M2 labeling in laminae VII and IX (McNeal et al., Journal of Comparative Neurology 518:586-621, 2010), the added effect of adjacent parietal cortex injury to the frontal motor lesion (F2P2 lesion) not only impedes a favorable compensatory neuroplastic response, but results in a substantial loss of M2 CSP terminals. This dramatic reversal of the CSP response suggests a critical trophic role for cortical somatosensory influence on spared ipsilesional frontal corticospinal projections, and that restoration of a favorable compensatory response will require therapeutic intervention. PMID:25349147

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

PubMed

Prowse, D M; Ktori, E N; Chandrasekaran, D; Prapa, A; Baithun, S

2008-02-01

Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.

Pathologic findings in red-tailed hawks (Buteo jamaicensis) and Cooper's hawks (Accipiter cooper) naturally infected with West Nile virus.

PubMed

Wünschmann, Arno; Shivers, Jan; Bender, Jeff; Carroll, Larry; Fuller, Susan; Saggese, Miguel; van Wettere, Arnaud; Redig, Pat

2004-09-01

Carcasses of 13 red-tailed hawks (RTHAs) and 11 Cooper's hawks (COHAs) were tested for West Nile virus (WNV) using WNV-specific reverse transcriptase-polymerase chain reaction (RT-PCR) on fresh brain tissue and WNV-specific immunohistochemistry (IHC) on various organs. Ten COHAs (91%) and 11 RTHAs (85%) were positive for WNV RNA by RT-PCR. All 11 COHAs (100%) and 10 RTHAs (77%) were positive for WNV antigen by IHC. A triad of inflammatory lesions, including chronic lymphoplasmacytic and histiocytic encephalitis, endophthalmitis, and myocarditis, was common in both species. In COHAs, the heart (54%), cerebrum (50%), and eye (45%) were the organs that most commonly contained WNV antigen. The amount of WNV antigen was usually small. In RTHAs, the kidney (38%), cerebrum (38%), cerebellum (38%), and eye (36%) were the organs most commonly containing WNV antigen. Unlike COHAs, larger amounts of WNV antigen were present in the cerebrum of RTHAs. WNV antigen was detected in similar cell populations in both species, including neurons of brain, spinal cord, and retina, pigmented epithelial cells of the retina, epithelial cells of renal medullary tubules, cardiomyocytes, endothelial cells and smooth muscle cells of arteries, dendritic cells of splenic lymph follicles, exocrine pancreatic cells, adrenal cells, and keratinocytes of the skin. The study presents strong evidence that WNV can cause a chronic fatal disease in RTHAs and COHAs. The lesion distribution of WNV infection in both species is variable, but inflammatory lesions are common, and a triad of lesions including encephalitis, myocarditis, and endophthalmitis is indicative of WNV infection in both species.

Tembusu-like flavivirus (Perak virus) as the cause of neurological disease outbreaks in young Pekin ducks.

PubMed

Homonnay, Zalán Gábor; Kovács, Edit Walkóné; Bányai, Krisztián; Albert, Mihály; Fehér, Enikő; Mató, Tamás; Tatár-Kis, Tímea; Palya, Vilmos

2014-01-01

A neurological disease of young Pekin ducks characterized by ataxia, lameness, and paralysis was observed at several duck farms in Malaysia in 2012. Gross pathological lesions were absent or inconsistent in most of the cases, but severe and consistent microscopic lesions were found in the brain and spinal cord, characterized by non-purulent panencephalomyelitis. Several virus isolates were obtained in embryonated duck eggs and in cell cultures (Vero and DF-1) inoculated with the brain homogenates of affected ducks. After exclusion of other viruses, the isolates were identified as a flavivirus by flavivirus-specific reverse transcription-polymerase chain reaction (RT-PCR) assays. Inoculation of 2-week-old Pekin ducks with a flavivirus isolate by the subcutaneous or intramuscular route resulted in typical clinical signs and histological lesions in the brain and spinal cord. The inoculated virus was detected by RT-PCR from organ samples of ducks with clinical signs and histological lesions. With a few days delay, the disease was also observed among co-mingled contact control birds. Phylogenetic analysis of NS5 and E gene sequences proved that the isolates were representatives of a novel phylogenetic group within clade XI (Ntaya virus group) of the Flavivirus genus. This Malaysian Duck Tembusu Virus (DTMUV), named Perak virus, has moderate genomic RNA sequence similarity to a related DTMUV identified in China. In our experiment the Malaysian strain of DTMUV could be transmitted in the absence of mosquito vectors. These findings may have implications for the control and prevention of this emerging group of flaviviruses.

Adaptive significance of right hemisphere activation in aphasic language comprehension

PubMed Central

Meltzer, Jed A.; Wagage, Suraji; Ryder, Jennifer; Solomon, Beth; Braun, Allen R.

2013-01-01

Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible (“The boy is eating the apple”) and reversible (“The boy is pushing the girl”) sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia. PMID:23566891

Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

PubMed

Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

2018-01-01

Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly, small interfering RNA-transfected knockdown of the migration inhibitory factor gene in methylglyoxal-treated skin keratinocytes increased expression of glyoxalase-I and intraepidermal nerve fibers in comparison with control small interfering RNA-transfected cells, which was decreased by induction of methylglyoxal. Conclusions Our findings suggest that migration inhibitory factor can aggravate diabetic neuropathy by suppressing glyoxalase-I and intraepidermal nerve fibers on the footpad skin lesions and provoke pain. Taken together, migration inhibitory factor might offer a pharmacological approach to alleviate pain syndromes in diabetic neuropathy.

Defect Characteristics of Reverse Hill-Sachs Lesions.

PubMed

Moroder, Philipp; Tauber, Mark; Scheibel, Markus; Habermeyer, Peter; Imhoff, Andreas B; Liem, Dennis; Lill, Helmut; Buchmann, Stefan; Wolke, Julia; Guevara-Alvarez, Alberto; Salmoukas, Katharina; Resch, Herbert

2016-03-01

Little scientific evidence regarding reverse Hill-Sachs lesions (RHSLs) in posterior shoulder instability exists. Recently, standardized measurement methods of the size and localization were introduced, and the biomechanical effect of the extent and position of the defects on the risk of re-engagement was determined. To analyze the characteristics and patterns of RHSLs in a large case series using standardized measurements and to interpret the results based on the newly available biomechanical findings. Case series; Level of evidence, 4. In this multicenter study, 102 cases of RHSLs in 99 patients were collected from 7 different shoulder centers between 2004 and 2013. Patient- as well as injury-specific information was gathered, and defect characteristics in terms of the size, localization, and depth index were determined on computed tomography or magnetic resonance imaging scans by means of standardized measurements. Additionally, the position (gamma angle) of the posterior defect margin as a predictor of re-engagement was analyzed. Three types of an RHSL were distinguished based on the pathogenesis and chronicity of the lesion: dislocation (D), locked dislocation (LD), and chronic locked dislocation (CLD). While the localization of the defects did not vary significantly between the subgroups (P = .072), their mean size differed signficantly (D: 32.6° ± 11.7°, LD: 49.4° ± 17.2°, CLD: 64.1° ± 20.7°; P < .001). The mean gamma angle as a predictor of re-engagement was similarly significantly different between groups (D: 83.8° ± 14.5°, LD: 96.5° ± 17.9°, CLD: 108.7° ± 18.4°; P < .001). The orientation of the posterior defect margin was consistently quite parallel to the humeral shaft axis, with a mean difference of 0.3° ± 8.1°. The distinction between the 3 different RHSL types based on the pathogenesis and chronicity of the defect helps identify defects prone to re-engagement. The gamma angle as a measurement of the position of the posterior defect margin and therefore a predictor of re-engagement varies significantly between the defect types. © 2016 The Author(s).

Safinamide: from molecular targets to a new anti-Parkinson drug.

PubMed

Caccia, C; Maj, R; Calabresi, M; Maestroni, S; Faravelli, L; Curatolo, L; Salvati, P; Fariello, R G

2006-10-10

Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and slowing disease progression. Of all remedies, levodopa remains the most effective for symptomatic relief, but the medical need for neuroprotectant drugs is still unfulfilled. Safinamide, currently in phase III clinical trials for the treatment of PD, is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted mice and reverses the waning motor response after prolonged levodopa treatment in 6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics, and is suitable for once-a-day administration. Therefore, safinamide may be used in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to test disease-modifying potential.

The loss of local HGF, an endogenous gastrotrophic factor, leads to mucosal injuries in the stomach of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakahira, Rie; Department of Neurosurgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2-E6, Suita 565-0871; Mizuno, Shinya

2006-03-24

The stomach is constantly exposed to mechanical and chemical stresses. Under persistent damages, epithelial cell proliferation is required to maintain mucosal integrity. Nevertheless, which ligand system(s) is physiologically involved in gastric defense remains unclear. Herein, we provide evidence that HGF is a key 'natural ligand' to reverse gastric injury. The injection of cisplatin in mice led to the loss of HGF in the gastric interstitium, associated with the decrease in proliferating epithelium and the progression of mucotitis. When c-Met tyrosine phosphorylation was abolished by anti-HGF IgG, mucosal cell proliferation became faint, leading to delayed recovery from mucotitis, and vice versamore » in cases of HGF supplementation. Our findings indicate that: (1) HGF/c-Met signal on mucosa is needed to restore gastric injuries; and (2) the loss of local HGF leads to manifestation of gastric lesions. This study provides a rationale that explains why HGF supplement is useful for reversing gastric diseases.« less

Reversal of CD8 T-Cell–Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor Tofacitinib

PubMed Central

Okiyama, Naoko; Furumoto, Yasuko; Villarroel, Vadim A; Linton, Jay T; Tsai, Wanxia L; Gutermuth, Jan; Ghoreschi, Kamran; Gadina, Massimo; O'Shea, John J; Katz, Stephen I

2014-01-01

The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-γ-inducible chemoattractants by keratinocytes, and IFN-γ-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell–mediated mucocutaneous diseases in patients with GVHD. PMID:24213371

A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension.

PubMed

Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

2016-04-01

A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances.

TOPICAL TENOFOVIR, A MICROBICIDE EFFECTIVE AGAINST HIV, INHIBITS HERPES SIMPLEX VIRUS-2 REPLICATION

PubMed Central

Andrei, Graciela; Lisco, Andrea; Vanpouille, Christophe; Introini, Andrea; Balestra, Emanuela; van den Oord, Joost; Cihlar, Tomas; Perno, Carlo-Federico; Snoeck, Robert; Margolis, Leonid; Balzarini, Jan

2011-01-01

SUMMARY The HIV reverse transcriptase inhibitor tenofovir, was recently formulated into a vaginal gel for use as a microbicide. In human trials, a 1% tenofovir gel inhibited HIV sexual transmission by 39% and surprisingly herpes simplex virus-2 (HSV-2) transmission by 51%. We demonstrate that the concentration achieved intravaginally with a 1% tenofovir topical gel has direct anti-herpetic activity. Tenofovir inhibits the replication of HSV clinical isolates in human embryonic fibroblasts, keratinocytes, and organotypic epithelial 3D-rafts, decreases HSV replication in human lymphoid and cervical tissues ex vivo, and delays HSV-induced lesions and death of topically treated HSV-infected mice. The active tenofovir metabolite inhibits HSV DNA-polymerase and HIV reverse transcriptase. Tenofovir must be topically administered to achieve concentrations, which are higher than systemic levels after oral treatment, that exert these dual antiviral effects. These findings indicate that a single topical treatment, like tenofovir, can inhibit the transmission of HIV and its co-pathogens. PMID:22018238

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

PubMed Central

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

2013-01-01

Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

Percutaneous epidural neurostimulation in modulation of paraplegic spasticity. Six case reports.

PubMed

Richardson, R R; Cerullo, L J; McLone, D G; Gutierrez, F A; Lewis, V

1979-01-01

Six cases of paraplegic, post-traumatic spasticity, alleviated by percutaneous epidural neurostimulation with temporary or permanent implanted neuroelectrodes from the L1 to L4 intervertebral levels are presented. Modulation of this spasticity and secondary beneficial physiological effects were achieved, including regulation of bowel regimens, production of sweating and piloerection below the level of the lesion, and morning erections. The main advantages of percutaneous epidural neurostimulation in modulating spasticity are the avoidance of destructive neurosurgical procedures, the regulation of secondary physiological and autonomic responses, the avoidance of antispasticity medications, and the reversibility of the neurostimulation procedure.

Femoral vessel injury by a nonlethal weapon projectile.

PubMed

Biagioni, Rodrigo Bruno; Miranda, Gustavo Cunha; Mota de Moraes, Leonardo; Nasser, Felipe; Burihan, Marcelo Calil; Ingrund, José Carlos

2018-06-01

Rubber projectiles are used as an alternative to metal bullets owing to their lower morbidity and mortality rate. There are few reports of vascular lesions of extremities caused by rubber projectiles in the literature. The authors report the case of a 37-year-old man who was the victim of a penetrating injury to the left thigh with a rubber projectile. He reported only pain at the site of the injury; pulses were decreased in the affected limb. After arteriography confirmed an injury to the superficial femoral artery, he underwent an arterial and venous femorofemoral bypass using a reversed contralateral saphenous vein.

Gasoline immersion injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simpson, L.A.; Cruse, C.W.

1981-01-01

Chemical burns and pulmonary complications are the most common problems encountered in the patient immersed in gasoline. Our patient demonstrated a 46-percent total-body-surface area, partial-thickness chemical burn. Although he did not develop bronchitis or pneumonitis, he did display persistent atelectasis, laryngeal edema, and subsequent upper airway obstruction. This had not previously been reported in gasoline inhalation injuries. Hydrocarbon hepatitis secondary to the vascular endothelial damage is apparently a reversible lesion with no reported long-term sequelae. Gasoline immersion injuries may be a series multisystem injury and require the burn surgeon to take a multisystem approach to its diagnosis and treatment.

[Repairing of soft tissue defect in leg by free vascularized thoracoumbilical flap with reversed flow].

PubMed

Xu, Y Q; Li, Z Y; Li, J

2000-11-01

To investigate the clinical effect of free vascularized thoracoumbilical flap with reversal flow in repairing the soft tissue defect in leg with tibia exposure. Forty-four casting mould specimens of leg arteries were studied firstly. Then 25 cases with soft tissue defect and tibia exposure in the proximal-middle segment of leg were adopted in this study. Among them, 18 cases had long distance thrombosis of the anterior tibial vessels or posterior tibial vessels due to traumatic lesion. The maximal size of defect was 28 cm x 11 cm and the minimal size of defect was 11 cm x 9 cm. In operation, the thoracoumbilical flap which was based on the inferior epigastric vessels was anastomosed to the distal end of the anterior tibial vessels or posterior tibial vessels. Anterior tibial artery, posterior tibial artery and fibular artery had rich communication branches in foot and ankle. All the flaps survived, the color and cosmetic result of them were good. The free vascularized thoracoumbilical flap with reversed flow is practical in repairing the soft tissue defect of leg with tibia exposure. Either the anterior tibial vessels or the posterior tibial vessels is normal, and the distal end of injured blood vessels is available, this technique can be adopted.

Elucidating the mechanism of posterior reversible encephalopathy syndrome: a case of transient blindness after central venous catheterization.

PubMed

Rao, Neal M; Raychev, Radoslav; Kim, Doojin; Liebeskind, David S

2012-11-01

Posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible symptoms including headache, visual disturbances, focal neurological deficits, altered mentation, and seizures. It has been associated with circumstances that may affect the cerebrovascular system, such as hypertension, eclampsia, and immunosuppression with calcineurin inhibitors. The underlying etiology of PRES has remained unclear; however, cerebrovascular autoregulatory dysfunction, hyperperfusion, and endothelial activation have been implicated. We describe a case of a young patient with lung transplant, who presented with headache, acute binocular blindness, and seizure immediately after infusion of saline through a peripherally inserted central catheter line, which inadvertently terminated cephalad in the left internal jugular vein, near the jugular foramen. Subsequent brain magnetic resonance imaging revealed vasogenic edematous lesions in a pattern consistent with PRES--a diagnosis supported by his constellation of symptoms, history of lung transplantation on tacrolimus immunosuppression, and relative hypertension. This is the first reported case describing the development of PRES after the insertion of a peripherally inserted central catheter line. The development of PRES in a typical high-risk patient immediately after cerebral venous outflow obstruction implicates the role of the cerebral venous system and provides potential insight into the mechanism of this disorder that remains of unclear pathogenesis.

Central-Variant Posterior Reversible Encephalopathy Syndrome with Albuminocytologic Dissociation.

PubMed

Lee, Sang-Woo; Lee, Seung-Jae

2018-01-01

Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible vasogenic brain edema which mainly involves the parieto-occipital lobes in various clinical settings. The main mechanism is known to be cerebral autoregulation failure and endothelial dysfunction leading to the disruption of the blood-brain barrier. We report the case of a 47-year-old woman with PRES which involved the brain stem and thalami, sparing the cerebral hemispheres. She was admitted to the emergency room because of acute-onset confusion. Her initial blood pressure was 270/220 mm Hg. Routine blood lab tests showed pleocytosis, hyperglycemia, and azotemia. Brain magnetic resonance imaging (MRI) showed a lesion of vasogenic edema involving nearly the whole area of pons, the left side of the midbrain, and the bilateral medial thalami. Cerebrospinal fluid (CSF) examination revealed an increased level of protein with normal white blood cell count. With conservative care, the patient markedly recovered 3 days after symptom onset, and a follow-up MRI confirmed complete resolution of the vasogenic edema. This case suggests that PRES can rarely involve the "central zone" only, sparing the cerebral hemispheres, which may be confused with other neurological diseases. Besides, the CSF albuminocytologic dissociation may suggest the disruption of the blood-brain barrier in patients with PRES.

COTIP: Cotton TILLING Platform, a Resource for Plant Improvement and Reverse Genetic Studies

PubMed Central

Aslam, Usman; Cheema, Hafiza M. N.; Ahmad, Sheraz; Khan, Iqrar A.; Malik, Waqas; Khan, Asif A.

2016-01-01

Cotton is cultivated worldwide for its white fiber, of which around 90% is tetraploid upland cotton (Gossypium hirsutum L.) carrying both A and D genome. Since centuries, yield increasing efforts for the cotton crop by conventional breeding approaches have caused an extensive erosion of natural genetic variability. Mutation based improvement strategies provide an effective way of creating new allelic variations. Targeting Induced Local Lesions IN Genomes (TILLING) provides a mutation based reverse genetic strategy to create and evaluate induced genetic variability at DNA level. Here, we report development and testing of TILLING populations of allotetraploid cotton (G. hirsutum) for functional genomic studies and mutation based enrichment of cotton genetic resources. Seed of two cotton cultivars “PB-899 and PB-900” were mutagenized with 0.3 and 0.2% (v/v) ethyl methanesulfonate, respectively. The phenotyping of M1 and M2 populations presented numerous mutants regarding the branching pattern, leaf morphology, disease resistance, photosynthetic lesions and flower sterility. Molecular screening for point mutations was performed by TILLING PCR aided CEL1 mismatch cleavage. To estimate the mutation frequency in the mutant genomes, five gene classes were TILLed in 8000 M2 plants of each var. “PB-899” and “PB-900.” These include actin (GhACT), Pectin Methyl Esterase (GhPME), sucrose synthase (GhSUS), resistance gene analog, and defense response gene (DRGs). The var. PB-899 was harboring 47% higher mutation induction rate than PB-900. The highest rate of mutation frequency was identified for NAC-TF5 (EU706348) of DRGs class, ranging from 1/58 kb in PB-899 to 1/105 kb in PB-900. The mutation screening assay revealed the presence of significant proportion of induced mutations in cotton TILLING populations such as 1/153 kb and 1/326 kb in var. “PB-899” and “PB-900,” respectively. The establishment of a cotton TILLING platform (COTIP) and data obtained from the resource TILLING population suggest its effectiveness in widening the genetic bases of cotton for improvement and utilizing it for subsequent reverse genetic studies of various genes. PMID:28082993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilat, E.; Kadar, T.; Levy, A.

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsantmore » effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.« less

Surface variations affecting human dental enamel studied using nanomechanical and chemical analysis

NASA Astrophysics Data System (ADS)

Dickinson, Michelle Emma

The enamel surface is the interface between the tooth and its ever changing oral environment. Cavity (caries) formation and extrinsic tooth staining are due, respectively, to degradation of the enamel structure under low pH conditions and interactions between salivary pellicle and dietary elements. Both of these occur at the enamel surface and are caused by the local environment changing the chemistry of the surface. The results can be detrimental to the enamel's mechanical integrity and aesthetics. Incipient carious lesions are the precursor to caries and form due to demineralisation of enamel. These carious lesions are a reversible structure where ions (e.g. Ca2+, F -) can diffuse in (remineralisation) to preserve the tooth's structural integrity. This investigation used controlled in vitro demineralisation and remineralisation to study artificial carious lesion formation and repair. The carious lesions were cross-sectioned and characterised using nanoindentation, electron probe micro-analysis and time of flight secondary ion mass spectrometry. Mechanical and chemical maps showed the carious lesion had a significantly reduced hardness and elastic modulus, and the calcium and phosphate content was lower than in sound enamel. Fluoride based remineralisation treatments gave a new phase (possibly fluorohydroxyapatite) within the lesion with mechanical properties higher than sound enamel. The acquired salivary pellicle is a protein-rich film formed by the physisorption of organic molecules in saliva onto the enamel surface. Its functions include lubrication during mastication and chemical protection. However, pellicle proteins react with dietary elements such as polyphenols (tannins in tea) causing a brown stain. This study has used in vitro dynamic nanoindentation and atomic force microscopy to examine normal and stained pellicles formed in vivo. The effects of polyphenols on the pellicle's mechanical properties and morphology have been studied. It was found that the initial adsorption of proteins occurred within 30 seconds of exposure to the oral cavity; fully mature pellicles develop in 2 hours. Polyphenol staining resulted in substantial changes in the morphology and mechanical properties of the pellicle. Specifically, staining gives pellicles consisting of large globules with high surface adhesion and a high loss tangent. These changes help explain why extrinsic stains are difficult to remove abrasively.

Multi-parametric monitoring and assessment of high-intensity focused ultrasound (HIFU) boiling by harmonic motion imaging for focused ultrasound (HMIFU): an ex vivo feasibility study

NASA Astrophysics Data System (ADS)

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E.

2014-03-01

Harmonic motion imaging for focused ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase shift during high energy HIFU treatment with tissue boiling. Forty three (n = 43) thermal lesions were formed in ex vivo canine liver specimens (n = 28). Two-dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10 s, 20 s and 30 s HIFU durations at three different acoustic powers of 8, 10, and 11 W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and passive cavitation detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δϕ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite the expectedly chaotic changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property changes throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with treatment duration, which was validated against pathology. In conclusion, multi-parametric HMIFU was shown capable of monitoring and mapping tissue viscoelastic response changes during and after HIFU boiling, some of which were independent of the acoustic parameter changes.

Modern concepts of caries measurement.

PubMed

Pitts, N B

2004-01-01

Following the consideration of several recent systematic and other reviews, there is a growing professional and scientific consensus that caries measurement methodology in caries clinical trials (CCT) should be updated to reflect progress made elsewhere in cariology. In this paper, therefore, "modern" means accepted in contemporary dental research and dental practice on the basis of sound research evidence--not necessarily new or requiring the use of new technology. Caries measurement should be seen in the context of the objectives of modern clinical caries management and the continuum of disease states, ranging from sub-surface carious changes through to more advanced lesions. Measurement concepts can be applied to at least three levels: the tooth surface, the individual, or the group/population. All are relevant to CCTs. Modern clinical caries management can be seen as comprised of seven discrete but linked steps (Steps 2, 3, and 4 are directly concerned with measurement.): (1) 'Caries detection' represents a yes/no decision as to whether caries is present; (2) lesion measurement assesses defined stages of the caries process, taking into account the histopatholgical morphology and appearance of different sizes and types of lesion and the diagnostic threshold(s) being used; (3) lesion monitoring by repeated measures at a series of examinations is used when lesions are less advanced than the stage judged to require operative intervention (A comparison of serial measurements permits the efficacy of preventive care aiming either to arrest or to reverse the lesion to be assessed.); (4) caries activity measures would be very valuable, but are relatively poorly developed and tested at present; (5) diagnosis, prognosis, and clinical decision-making are the important human processes in which all the information obtained from steps 1 to 4 is synthesised; (6) interventions/treatments, both preventive and operative, are now routinely used for caries management; and (7) outcome of caries control/management assesses caries management by examining evidence on the long-term outcomes. A challenge for the future is to define a range of optimal caries measurement methods--in use or in development in recent trials, in clinical practice, and/or in caries epidemiology--that will best contribute to more efficient, modern caries clinical trials.

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.

PubMed

Dubey, Jitender P; Ferreira, Leandra R; Alsaad, Mohammad; Verma, Shiv K; Alves, Derron A; Holland, Gary N; McConkey, Glenn A

2016-01-01

The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations.

Multi-parametric monitoring and assessment of High Intensity Focused Ultrasound (HIFU) boiling by Harmonic Motion Imaging for Focused Ultrasound (HMIFU): An ex vivo feasibility study

PubMed Central

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E.

2014-01-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase-shift during high energy HIFU treatment with tissue boiling. Forty three (n=43) thermal lesions were formed in ex vivo canine liver specimens (n=28). Two dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10-s, 20-s and 30-s HIFU durations at three different acoustic powers of 8, 10, and 11W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and Passive Cavitation Detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δφ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite unpredictable changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property change throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with treatment duration, which was validated against pathology. In conclusion, multi-parametric HMIFU was shown capable of monitoring and mapping tissue viscoelastic response changes during and after HIFU boiling, some of which were independent of the acoustic parameter changes. PMID:24556974

Multi-parametric monitoring and assessment of high-intensity focused ultrasound (HIFU) boiling by harmonic motion imaging for focused ultrasound (HMIFU): an ex vivo feasibility study.

PubMed

Hou, Gary Y; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E

2014-03-07

Harmonic motion imaging for focused ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase shift during high energy HIFU treatment with tissue boiling. Forty three (n = 43) thermal lesions were formed in ex vivo canine liver specimens (n = 28). Two-dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10 s, 20 s and 30 s HIFU durations at three different acoustic powers of 8, 10, and 11 W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and passive cavitation detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δϕ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite the expectedly chaotic changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property changes throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with treatment duration, which was validated against pathology. In conclusion, multi-parametric HMIFU was shown capable of monitoring and mapping tissue viscoelastic response changes during and after HIFU boiling, some of which were independent of the acoustic parameter changes.

Hepatic steatosis background in chronic hepatitis B and C - significance of similarities and differences.

PubMed

Moroşan, Eugenia; Mihailovici, Maria Sultana; Giuşcă, Simona Eliza; Cojocaru, Elena; Avădănei, Elena Roxana; Căruntu, Irina Draga; Teleman, Sergiu

2014-01-01

The aim of our study was to investigate comparatively the steatotic background in viral chronic hepatitis B, C and mixed types, in correlation with the severity degree of specific liver lesions. The study group consisted of 1206 liver biopsy specimens, etiologically diagnosed as hepatitis C - 1021 (84.66%) cases, hepatitis B - 100 (8.29%) cases, hepatitis B and C - 39 (3.23%) cases, hepatitis B and D - 39 (3.23%) cases, hepatitis C and toxicity - six (0.49%) cases, hepatitis B, C and D - one case (0.08%). The histopathological assessment focused on the steatotic lesions associated with inflammation and fibrosis. The cases were classified according to necrosis and inflammatory activity (score between 0-12) and fibrosis (score between 0-4). Our data indicates significant association of steatotic lesions in hepatitis C (76.59%) as opposed to other types of viral hepatitis. In mixed hepatitis B and C, steatotic lesions are more frequent (66.66%) than in chronic hepatitis B (47%) and in mixed chronic B and D hepatitis (48.72%). Steatosis was present in all cases with chronic hepatitis C and associated toxicity. These observations confirm the important aggressiveness of hepatitis C virus as opposed to hepatitis B and D virus. The analysis of the pattern of steatosis in correlation with necrosis and inflammatory activity and fibrosis, respectively, lead to the identification of certain specific elements. Thus, for all types of hepatitis, steatosis is associated predominantly with moderate severity (score 6-8) and progressive expansion of fibrosis (score 2-3). The presence of steatosis does not define hepatic lesions with severe inflammation (score 9-12) nor those with extended fibrosis (score 4). The type of steatosis present is mostly macrovesicular, the transformation into lipid cysts being uncommon. Based on the scoring systems applied in the evaluation of the entire investigated study group, we believe that a possible inclusion of a quantifiable criterion for steatosis could be beneficial in order to complete the characterization of the severity of the lesions, from the point of view of the potential for future evolution, reversible or irreversible.

The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO).

PubMed

Magierowska, Katarzyna; Magierowski, Marcin; Surmiak, Marcin; Adamski, Juliusz; Mazur-Bialy, Agnieszka Irena; Pajdo, Robert; Sliwowski, Zbigniew; Kwiecien, Slawomir; Brzozowski, Tomasz

2016-03-24

Carbon monoxide (CO) produced by heme oxygenase (HO)-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1-10 mg/kg oral gavage (i.g.)), RuCl₃ (1 mg/kg i.g.), zinc protoporphyrin IX (ZnPP) (10 mg/kg intraperitoneally (i.p.)), hemin (1-10 mg/kg i.g.) and CORM-2 (1 mg/kg i.g.) combined with N(G)-nitro-l-arginine (l-NNA, 20 mg/kg i.p.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p.), indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.), and celecoxib (10 mg/kg i.g.) affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS). Gastric blood flow (GBF), the number of gastric lesions and gastric CO and nitric oxide (NO) contents, blood carboxyhemoglobin (COHb) level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α), tumor necrosis factor α (TNF-α), cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) were determined. CORM-2 (1 mg/kg i.g.) and hemin (10 mg/kg i.g.) significantly decreased WRS lesions while increasing GBF, however, RuCl₃ was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO's hyperemic and anti-inflammatory properties, but is independent of NO.

Interleukin (IL)-8 and IL-36γ but not IL-36Ra are related to acrosyringia in pustule formation associated with palmoplantar pustulosis.

PubMed

Xiaoling, Y; Chao, W; Wenming, W; Feng, L; Hongzhong, J

2018-06-12

Palmoplantar pustulosis (PPP) is a refractory, nonbacterial impetigo confined to the palms and soles. Its pathogenesis is still obscure, but it may be associated with the large eccrine sweat glands and pores of palmoplantar skin. PPP is considered to be a localized pustular psoriasis. Interleukin (IL)-8, IL-36γ and IL-36Ra play important roles in the pathogenesis of pustular psoriasis, but their role in PPP is unclear. To evaluate IL-8, IL-36γ and IL-36Ra expression in PPP, and their relationship with acrosyringia and pustule formation. mRNA expression was quantified in skin samples from patients with PPP (n = 7), patients with psoriasis vulgaris (PSV; n = 8) and healthy controls (HCs) (n = 6) by reverse-transcription-real-time PCR. Protein expression was characterized by immunohistochemistry (PPP, n = 17; PSV, n = 14; HCs, n = 12). Sweat ducts, including acrosyringia, were stained for epithelial membrane antigen (EMA). IL-8 mRNA and protein were markedly increased in PPP lesions compared with PSV lesions or HC skin. IL-36γ mRNA and protein were significantly more abundant in PPP lesions than in HC skin. IL-36Ra mRNA was significantly overexpressed in PPP lesions compared with HC skin, but there was no difference in IL-36Ra protein between PPP, PSV and HCs. IL-8 was abundantly expressed by neutrophils in PPP pustules, while IL36Ra was localized in the keratinocytes of PPP, PSV and HC skin. IL-36γ and EMA were colocalized in cells surrounding PPP pustules, and IL-36γ was also expressed in sweat duct cells in the dermis. IL-8, IL-36γ and IL-36Ra are overexpressed in PPP lesions. IL-8, IL-36γ and acrosyringia, rather than IL-36Ra, are associated with pustule formation in PPP. © 2018 British Association of Dermatologists.

Systemic administration of dizocilpine maleate (MK-801) or L-dopa reverses the increases in GAD65 and GAD67 mRNA expression in the globus pallidus in a rat hemiparkinsonian model.

PubMed

Bacci, Jean-Jacques; Salin, Pascal; Kerkerian-Le Goff, Lydia

2002-12-15

This study examined the consequences of systemic treatment with either L-dopa or MK-801 on the levels of mRNAs encoding the 65 and 67 kDa isoforms of glutamate decarboxylase (GAD65 and GAD67) in the striatum and globus pallidus (GP) of rats rendered hemiparkinsonian by intranigral 6-hydroxydopamine injection. GADs mRNA levels were assessed by means of in situ hybridization histochemistry. In the striatum, dopamine denervation resulted in increased GAD67 mRNA levels at the rostral and caudal levels, whereas GAD65 showed selective increase at the caudal level. L-dopa and MK-801 treatments showed differential effects on the two GAD isoform levels in rats with 6-hydroxydopamine lesion. The lesion-induced increases in GAD67 transcripts were potentiated by L-dopa but unaffected by MK-801, whereas the increases in GAD65 were suppressed by MK-801 but unaffected by L-dopa. These data suggest a heterogeneity of glutamate-dopamine interaction in the anteroposterior extent of the striatum and show that NMDA-mediated mechanisms are involved in the 6-hydroxydopamine lesion-induced transcriptional changes in striatal GAD65 but not GAD67. In GP, the 6-OHDA lesion elicited increases in both GAD65 and GAD67 mRNA levels. L-dopa or MK-801 treatment suppressed the lesion-induced augmentations in the two GADs mRNA levels. These results indicate that dopamine denervation-induced changes in the functional activity of GP neurons involve both dopamine and glutamate NMDA receptor-mediated mechanisms. Comparison between the effects of L-dopa and MK-801 treatments on markers of the activity of striatal and pallidal GABA neurons further suggest that the impact of these treatments at the GP level do not depend solely on the striatopallidal input. Copyright 2002 Wiley-Liss, Inc.

Brain stem venous congestion due to dural arteriovenous fistulas of the cavernous sinus.

PubMed

Kai, Y; Hamada, J I; Morioka, M; Yano, S; Ushio, Y

2004-10-01

Venous congestion of the brain stem due to dural arteriovenous fistulas (DAVFs) in the cavernous sinus is rare and presents therapeutic challenges. To assess the prognosis of patients with symptomatic DAVFs and brain stem dysfunction, we evaluated the degree of venous ischemia by examining pre- and post-treatment magnetic resonance images (MRI) in 2 patients presenting with venous congestion of the brain stem. A 56-year-old woman with left hemiparesis and a 70-year-old woman with gait disturbance attributable to right cavernous sinus DAVFs were referred to our hospital. In both cases, T2-weighted magnetic resonance imaging (MRI) disclosed a hyperintensity lesion in the brainstem due to venous congestion. Both patients underwent open surgery for direct embolization of the cavernous sinus because there were no approach routes for transvenous embolization. The patient whose pretreatment MRI demonstrated Gd enhancement continued to manifest neurological deficits and persistence of the abnormal hyperintensity on post-treatment T2-weighted MRI. In the other patient whose pretreatment MRI showed no Gd enhancement, treatment produced a complete response of her neurological deficit and disappearance of the abnormal hyperintensity area. We tentatively conclude that lesions corresponding to hyperintensity areas on non-Gd-enhanced, T2-weighted MRI may reflect a reversible condition whereas lesions identified as hyperintense areas on GD-enhanced T2-weighted MRI may be indicative of irreversibility.

Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation.

PubMed

Duan, Chong; Perez-Torres, Carlos J; Yuan, Liya; Engelbach, John A; Beeman, Scott C; Tsien, Christina I; Rich, Keith M; Schmidt, Robert E; Ackerman, Joseph J H; Garbow, Joel R

2017-05-01

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P < 0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P < 0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation.

Mefloquine adverse effects with atypical facial lesions in an overweight patient.

PubMed

Descloux, Elodie; De Monbrison, Frédérique; Basselin, Cécile; Vial, Thierry; Peyron, François

2010-09-01

The recommended dosage of mefloquine to treat Plasmodium falciparum infection is 25 mg/kg, with no recommendation for dosage exceeding 1500 mg. We describe an original case of adverse reaction to mefloquine in an overweight patient. Case report. A 32-year-old woman weighing 139 kg presented with uncomplicated P. falciparum infection after returning from Cameroon. She received 3250 mg of mefloquine (i.e. 23 mg/kg) administered in four doses. On day 2, she developed neuropsychiatric disorders and facial lesions. Nasal mucocutaneous vesicles and bullae, depressive mood, mild thrombocytopenia and hepatic cytolysis were evidenced. Parasitemia was negative. Recovery was complete on day 17. High mefloquine serum levels were measured (8.030 mg/L on day 3, 6.880 mg/L on day 8, and 3.370 mg/L on day 17). The causal relationship between mefloquine and the occurrence of these adverse effects is probable. However, as no viral or bacteriological investigations were performed, the drug responsibility remains uncertain. Mefloquine-induced bullous and facial lesions reversible upon drug withdrawal have already been described. The associated neuropsychiatric symptoms were strongly suggestive of mefloquine adverse effects, as such events are more frequently observed in cases of overdosage. Our case emphasizes the difficulties of dosage adaptation in overweight patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Can anti-Vascular Endothelial Growth Factor Antibody Reverse Radiation Necrosis? A Preclinical Investigation

PubMed Central

Duan, Chong; Perez-Torres, Carlos J; Yuan, Liya; Engelbach, John A; Beeman, Scott C; Tsien, Christina I; Rich, Keith M; Schmidt, Robert E; Ackerman, Joseph JH; Garbow, Joel R

2017-01-01

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife PerfexionTM and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4 to 12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P<0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P<0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation. PMID:28425047

Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents

PubMed Central

Szabo, Eva; Miller, Mark Steven; Lubet, Ronald A.; You, Ming; Wang, Yian

2017-01-01

Due to exposure to environmental toxicants, a “field cancerization” effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively. Activated MYC signaling was also present in premalignant and tumor tissues from human lung SCC patients. In addition, we identified a key microRNA, mmu-miR-449c-5p, whose suppression significantly up-regulated Myc expression in the normal bronchial airway epithelial cells of mice with early stage SCC lesions. We developed a novel bronchial genomic classifier in mice and validated it in humans. In the classifier, Ppbp (pro-platelet basic protein) was overexpressed 115 fold in the bronchial airways of mice with preneoplastic lung SCC lesions. This is the first report that demonstrates Ppbp as a novel biomarker in the bronchial airway for lung cancer diagnosis. PMID:27935865

Functional connectivity: integrating behavioral, diffusion tensor imaging, and functional magnetic resonance imaging data sets.

PubMed

Baird, Abigail A; Colvin, Mary K; Vanhorn, John D; Inati, Souheil; Gazzaniga, Michael S

2005-04-01

In the present study, we combined 2 types of magnetic resonance technology to explore individual differences on a task that required the recognition of objects presented from unusual viewpoints. This task was chosen based on previous work that has established the necessity of information transfer from the right parietal cortex to the left inferior cortex for its successful completion. We used reaction times (RTs) to localize regions of cortical activity in the superior parietal and inferior frontal regions (blood oxygen level-dependent [BOLD] response) that were more active with longer response times. These regions were then sampled, and their signal change used to predict individual differences in structural integrity of white matter in the corpus callosum (using diffusion tensor imaging). Results show that shorter RTs (and associated increases in BOLD response) are associated with increased organization in the splenium of the corpus callosum, whereas longer RTs are associated with increased organization in the genu.

Loss-of-function mutation in RUSC2 causes intellectual disability and secondary microcephaly.

PubMed

Alwadei, Ali H; Benini, Ruba; Mahmoud, Adel; Alasmari, Ali; Kamsteeg, Erik-Jan; Alfadhel, Majid

2016-12-01

Inherited aberrancies in intracellular vesicular transport are associated with a variety of neurological and non-neurological diseases. RUSC2 is a gene found on chromosome 9p13.3 that codes for iporin, a ubiquitous protein with high expression in the brain that interacts with Rab proteins (GTPases implicated in intracellular protein trafficking). Although mutations in Rab proteins have been described as causing brain abnormalities and intellectual disability, until now no disease-causing mutations in RUSC2 have ever been reported in humans. We describe, to our knowledge for the first time, three patients with inherited homozygous nonsense mutations identified in RUSC2 on whole-exome sequencing. All three patients had central hypotonia, microcephaly, and moderate to severe intellectual disability. Two patients had additional features of early-onset epilepsy and absence of the splenium. This report adds to the ever-expanding landscape of genetic causes of intellectual disability and increases our understanding of the cellular processes underlying this important neurological entity. © 2016 Mac Keith Press.

Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

PubMed Central

Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

Long-term effects of neonatal medial temporal ablations on socioemotional behavior in monkeys

PubMed Central

Málková, Ludise; Mishkin, Mortimer; Suomi, Stephen J.; Bachevalier, Jocelyne

2010-01-01

Socioemotional abnormalities, including low levels of social interaction and high levels of self-directed activity, were reported when rhesus monkeys with neonatal ablations of either the medial temporal lobe (AH) or the inferior temporal cortex (TE) were paired with unoperated peers at two and six months of age, though these abnormalities were more severe in the AH group (Bachevalier et al., 2001). As they reached adulthood (Experiment 1), the same monkeys were re-evaluated in the same dyads and their reactivity to novel toys, social status, and reactions to separation from age-matched peers were also assessed. Group TE now showed few if any of the abnormal behaviors observed when they were infants. By contrast, Group AH continued to display low levels of social interaction, high levels of self-directed activity and submissive behavior, and reduced responses to separation, although they reacted normally to novel toys. To determine whether this degree of socioemotional impairment was less severe than that produced by the same damage in adulthood, we assessed dyadic social interactions of monkeys raised until adulthood in laboratory conditions similar to those of the earlier groups and then given the AH ablation (Experiment 2). Two months postoperatively these adult-lesioned monkeys showed a small reduction in social interactions that became more pronounced six months postoperatively, yet remained less severe than that seen in the infant-lesioned monkeys. Also, except for an increase in food and water consumption throughout this 6-month period, they showed no other socioemotional effects. The finding that neonatal AH lesions produce more severe socioemotional disturbances than the same lesion in adulthood is the reverse of the effect commonly reported for other cognitive functions after cerebral damage. PMID:21133531

Neurotoxic response of infant monkeys to methylmercury.

PubMed

Willes, R F; Truelove, J F; Nera, E A

1978-02-01

Four infant monkeys were dosed orally with 500 microgram Hg/kg body wt./day /as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28--29 days of treatment; the blood Hg levels were 8.0--9.4 microgram Hg/g blood. Dosing was terminated at 28--29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35--43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver (55.8 +/- 3.2 microgram Hg/g) followed by occipital cortex (35.6 +/- 4.8 microgram Hg/g) renal cortex (32.8 +/- 1.6 microgram Hg/g). The frontal and temporal cortices had 27.0 +/- 3.4 and 29.6 +/- 4.9 microgram Hg/g respectively while the cerebellar Hg concentration averaged 13.0 +/- 1.5 microgram Hg/g. The mean blood/brain ratio was 0.21 +/- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

PubMed Central

Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens

2013-01-01

Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS. PMID:24109235

Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours.

PubMed

Lane, E L; Cheetham, S C; Jenner, P

2005-01-01

BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with l-3,4-dihydroxyphenylalanine methyl ester (L-dopa). Acute administration of BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both L-dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In L-dopa-treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by L-dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.

The formation of catalytically competent enzyme-substrate complex is not a bottleneck in lesion excision by human alkyladenine DNA glycosylase.

PubMed

Kuznetsov, N A; Kiryutin, A S; Kuznetsova, A A; Panov, M S; Barsukova, M O; Yurkovskaya, A V; Fedorova, O S

2017-04-01

Human alkyladenine DNA glycosylase (AAG) protects DNA from alkylated and deaminated purine lesions. AAG flips out the damaged nucleotide from the double helix of DNA and catalyzes the hydrolysis of the N-glycosidic bond to release the damaged base. To understand better, how the step of nucleotide eversion influences the overall catalytic process, we performed a pre-steady-state kinetic analysis of AAG interaction with specific DNA-substrates, 13-base pair duplexes containing in the 7th position 1-N6-ethenoadenine (εA), hypoxanthine (Hx), and the stable product analogue tetrahydrofuran (F). The combination of the fluorescence of tryptophan, 2-aminopurine, and 1-N6-ethenoadenine was used to record conformational changes of the enzyme and DNA during the processes of DNA lesion recognition, damaged base eversion, excision of the N-glycosidic bond, and product release. The thermal stability of the duplexes characterized by the temperature of melting, T m , and the rates of spontaneous opening of individual nucleotide base pairs were determined by NMR spectroscopy. The data show that the relative thermal stability of duplexes containing a particular base pair in position 7, (T m (F/T) < T m (εA/T) < T m (Hx/T) < T m (A/T)) correlates with the rate of reversible spontaneous opening of the base pair. However, in contrast to that, the catalytic lesion excision rate is two orders of magnitude higher for Hx-containing substrates than for substrates containing εA, proving that catalytic activity is not correlated with the stability of the damaged base pair. Our study reveals that the formation of the catalytically competent enzyme-substrate complex is not the bottleneck controlling the catalytic activity of AAG.

The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions.

PubMed

Hessam, S; Sand, M; Skrygan, M; Bechara, Falk G

2017-09-01

Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

PubMed

Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

2007-04-01

There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke

PubMed Central

Vahid-Ansari, F; Lagace, D C; Albert, P R

2016-01-01

Post-stroke depression (PSD) is a common outcome following stroke that is associated with poor recovery. To develop a preclinical model of PSD, we targeted a key node of the depression–anxiety circuitry by inducing a unilateral ischemic lesion to the medial prefrontal cortex (mPFC) stroke. Microinjection of male C57/BL6 mice with endothelin-1 (ET-1, 1600 pmol) induced a small (1 mm3) stroke consistently localized within the left mPFC. Compared with sham control mice, the stroke mice displayed a robust behavioral phenotype in four validated tests of anxiety including the elevated plus maze, light–dark, open-field and novelty-suppressed feeding tests. In addition, the stroke mice displayed depression-like behaviors in both the forced swim and tail suspension test. In contrast, there was no effect on locomotor activity or sensorimotor function in the horizontal ladder, or cylinder and home cage activity tests, indicating a silent stroke due to the absence of motor abnormalities. When re-tested at 6 weeks post stroke, the stroke mice retained both anxiety and depression phenotypes. Surprisingly, at 6 weeks post stroke the lesion site was infiltrated by neurons, suggesting that the ET-1-induced neuronal loss in the mPFC was reversible over time, but was insufficient to promote behavioral recovery. In summary, unilateral ischemic lesion of the mPFC results in a pronounced and persistent anxiety and depression phenotype with no evident sensorimotor deficits. This precise lesion of the depression circuitry provides a reproducible model to study adaptive cellular changes and preclinical efficacy of novel interventions to alleviate PSD symptoms. PMID:27483381

Hippocampal P3-like auditory event-related potentials are disrupted in a rat model of cholinergic degeneration in Alzheimer's disease: reversal by donepezil treatment.

PubMed

Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe; Bastlund, Jesper Frank

2014-01-01

P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related to several psychiatric and neurological diseases, e.g., Alzheimer's disease (AD). However, only a very limited number of rodent studies have addressed the back-translational validity of the P3-like ERPs as suitable markers of cognition. Thus, the potential of rodent P3-like ERPs to predict pro-cognitive effects in humans remains to be fully validated. The current study characterizes P3-like ERPs in the 192-IgG-SAP (SAP) rat model of the cholinergic degeneration associated with AD. Following training in a combined auditory oddball and lever-press setup, rats were subjected to bilateral intracerebroventricular infusion of 1.25 μg SAP or PBS (sham lesion) and recording electrodes were implanted in hippocampal CA1. Relative to sham-lesioned rats, SAP-lesioned rats had significantly reduced amplitude of P3-like ERPs. P3 amplitude was significantly increased in SAP-treated rats following pre-treatment with 1 mg/kg donepezil. Infusion of SAP reduced the hippocampal choline acetyltransferase activity by 75%. Behaviorally defined cognitive performance was comparable between treatment groups. The present study suggests that AD-like deficits in P3-like ERPs may be mimicked by the basal forebrain cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup.

Depth and activity of carious lesions as indicators for the regenerative potential of dental pulp after intervention.

PubMed

Bjørndal, Lars; Demant, Sune; Dabelsteen, Sally

2014-04-01

Studies on dental regeneration involving interventions for pulp therapy such as regeneration and revascularization procedures are promising for the injured tooth; however, a complete replication of the original pulp tissue does not seem to take place. In cases in which we wish to preserve or maintain parts of the pulp during treatment, it is apparent that the effectiveness of healing or biological regeneration is dependent on the degree of inflammation of the pulp tissue. Thus, the control or prevention of a pulp infection is still a major issue for the clinicians. Data indicate that the typical reason for performing endodontic treatment is deep caries. The biological concept of vital pulp therapy associated with deep caries takes the treatment and evaluation of the unexposed as well as the exposed pulp into account. Interestingly, the clinical diagnosis is typically the same. Deep caries with reversible pulpitis may receive differing treatments such as excavation procedures aiming to avoid pulp exposure or more pulp invasive treatments such as pulp capping or pulpotomy. This should not be the case. Consequently, huge treatment variation is noted among clinicians based on the same caries diagnosis. Which treatment should be selected? High-quality trials are needed, and it is important to obtain information on the actual lesion depth and an estimate of the lesion activity before treatment. These may be basic indicators for the regenerative potential of dental pulp. Recent clinical trials dealing with the treatment of deep caries lesion are discussed, including pulp invasive and noninvasive concepts, to attempt to solve the task of getting the best clinical outcome for adult patients. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Proximal versus distal protection during carotid artery stenting: analysis of the two treatment approaches and associated clinical outcomes.

PubMed

Mokin, Maxim; Dumont, Travis M; Chi, Joan Mihyun; Mangan, Connor J; Kass-Hout, Tareq; Sorkin, Grant C; Snyder, Kenneth V; Hopkins, L Nelson; Siddiqui, Adnan H; Levy, Elad I

2014-01-01

Cerebral protection device utilization during carotid artery stenting (CAS) has been shown to decrease risk of perioperative stroke. The two most commonly used devices are distal filters and proximal protection devices, which allow blood flow cessation or flow reversal. The goal of the present study was to examine anatomic and morphologic characteristics of the treated lesions using each type of cerebral protection device and compare clinical 30-day adverse event rates between the two cerebral protection groups. We conducted a single-center, retrospective review of consecutive CAS cases with proximal protection devices that were matched with CAS cases using distal filter protection devices based on indication (symptomatic vs. asymptomatic), age, and gender. We reviewed clinical, anatomic, and morphologic characteristics of the stented lesions in cases of proximal or distal protection and also studied the rate of major adverse events within the first 30 days after the procedure. We identified a total of 70 patients treated with proximal protection devices who were matched in a blinded fashion to 70 cases with distal protection. There was a significantly higher number of high-risk lesions in patients who had CAS using proximal protection devices (P = 0.009). There was no significant difference in overall frequency of 30-day adverse outcomes (transient ischemic attack/stroke/reperfusion hemorrhage/death) between the two groups (P = 1.0). Our study is the first attempt (to our knowledge) to review and compare anatomic and morphologic characteristics of the stented lesions in cases of proximal versus distal protection for CAS. Our data indicate that in properly selected patients both approaches could be equally safe and effective. Copyright © 2014 Elsevier Inc. All rights reserved.

Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

PubMed

Dos Reis Lívero, Francislaine Aparecida; da Silva, Luisa Mota; Ferreira, Daniele Maria; Galuppo, Larissa Favaretto; Borato, Debora Gasparin; Prando, Thiago Bruno Lima; Lourenço, Emerson Luiz Botelho; Strapasson, Regiane Lauriano Batista; Stefanello, Maria Élida Alves; Werner, Maria Fernanda de Paula; Acco, Alexandra

2016-09-01

Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

Are Vocal Alterations Caused by Smoking in Reinke's Edema in Women Entirely Reversible After Microsurgery and Smoking Cessation?

PubMed

Martins, Regina Helena Garcia; Tavares, Elaine Lara Mendes; Pessin, Adriana Bueno Benito

2017-05-01

Reinke's edema is a benign lesion of the vocal folds that affects chronic smokers, especially women. The voice becomes hoarse and virilized, and the treatment is microsurgery. However, even after surgery and smoking cessation, many patients remain with a deep and hoarse voice. The aim of the present study was to compare pre- and postoperative acoustic and perceptual-auditory vocal analyses of women with Reinke's edema and of women in the control group, who were non-smokers. A total of 20 women with videolaryngoscopy diagnosis of Reinke's edema who underwent laryngeal microsurgery were evaluated pre- and postoperatively (6 months) by videolaryngoscopy, acoustic voice, and perceptual-auditory analyses (General degree of dysphonia, Roughness, Breathiness, Asthenia, Strain, and Instability [GRBASI] scale), and the maximum phonation times were calculated. The pre- and postoperative parameters of the women with Reinke's edema were compared with those of the control group of women with no laryngeal lesions, smoking habit, or vocal symptoms. Acoustic vocal perceptual-auditory analyses and the maximum phonation time of women with Reinke's edema improved significantly in the postoperative evaluations; nevertheless, 6 months after surgery, their voices became worse than the voices of the women from the control group. Abnormalities caused by smoking in Reinke's edema in women are not fully reversible with surgery and smoking cessation. One explanation would be the presence of possible structural alterations in fibroblasts caused by the toxicity of cigarette components, resulting in the uncontrolled production of fibrous matrix in the lamina propria, and preventing complete vocal recovery. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease.

PubMed

Sagredo, Onintza; Pazos, M Ruth; Satta, Valentina; Ramos, José A; Pertwee, Roger G; Fernández-Ruiz, Javier

2011-09-01

We studied whether combinations of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotection in rat models of Huntington's disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of Δ(9)-THC- and CBD-enriched botanical extracts. The issue was also studied in malonate-lesioned rats. The administration of Δ(9)-THC- and CBD-enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of CB(1) receptor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of Δ(9)-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB(1) and CB(2) receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1:1 combination of Δ(9)-THC and CBD. Finally, this combination also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies. Copyright © 2011 Wiley-Liss, Inc.

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

PubMed

Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

2015-01-01

Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

Effects of discontinuing a high-fat diet on mitochondrial proteins and 6-hydroxydopamine-induced dopamine depletion in rats.

PubMed

Ma, Delin; Shuler, Jeffrey M; Raider, Kayla D; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Stanford, John A

2015-07-10

Diet-induced obesity can increase the risk for developing age-related neurodegenerative diseases including Parkinson's disease (PD). Increasing evidence suggests that mitochondrial and proteasomal mechanisms are involved in both insulin resistance and PD. The goal of this study was to determine whether diet intervention could influence mitochondrial or proteasomal protein expression and vulnerability to 6-Hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine (DA) depletion in rats' nigrostriatal system. After a 3 month high-fat diet regimen, we switched one group of rats to a low-fat diet for 3 months (HF-LF group), while the other half continued with the high-fat diet (HF group). A chow group was included as a control. Three weeks after unilateral 6-OHDA lesions, HF rats had higher fasting insulin levels and higher Homeostasis model assessment of insulin resistance (HOMA-IR), indicating insulin resistance. HOMA-IR was significantly lower in HF-LF rats than HF rats, indicating that insulin resistance was reversed by switching to a low-fat diet. Compared to the Chow group, the HF group exhibited significantly greater DA depletion in the substantia nigra but not in the striatum. DA depletion did not differ between the HF-LF and HF group. Proteins related to mitochondrial function (such as AMPK, PGC-1α), and to proteasomal function (such as TCF11/Nrf1) were influenced by diet intervention, or by 6-OHDA lesion. Our findings suggest that switching to a low-fat diet reverses the effects of a high-fat diet on systemic insulin resistance, and mitochondrial and proteasomal function in the striatum. Conversely, they suggest that the effects of the high-fat diet on nigrostriatal vulnerability to 6-OHDA-induced DA depletion persist. Copyright © 2015 Elsevier B.V. All rights reserved.

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

PubMed Central

Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane

2015-01-01

Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson’s disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice.

PubMed

Santos Cerqueira, Gilberto; dos Santos e Silva, Gabriela; Rios Vasconcelos, Emiliano; Fragoso de Freitas, Ana Paula; Arcanjo Moura, Brinell; Silveira Macedo, Danielle; Lopes Souto, Augusto; Barbosa Filho, José Maria; de Almeida Leal, Luzia Kalyne; de Castro Brito, Gerly Anne; Souccar, Caden; de Barros Viana, Glauce Socorro

2012-05-15

This study investigates the gastroprotective effects of hecogenin, a steroid saponin isolated from Agave sisalana, on experimental models of gastric ulcer. Male Swiss mice were used in the models of ethanol- and indometacin-induced gastric ulcer. To clarify the hecogenin mechanism of action, the roles of nitric oxide (NO), sulfhydryls (GSH), K⁺(ATP) channels and prostaglandins were also investigated, and measurements of lipid peroxidation (TBARS assay) and nitrite levels in the stomach of hecogenin-treated and untreated animals were performed. Furthermore, the effects of hecogenin on myeloperoxidase (MPO) release from human neutrophils were assessed in vitro. Our results showed that hecogenin (3.1, 7.5, 15, 30, 60 and 90 mg/kg, p.o.) acutely administered, before ethanol or indomethacin, exhibited a potent gastroprotective effect. Although the pretreatments with L-NAME, an iNOS inhibitor, and capsazepine, a TRPV1 receptor agonist, were not able to reverse the hecogenin effect, this was reversed by glibenclamide, a K⁺(ATP) blocker, and indomethacin in the model of ethanol-induced gastric lesions. The hecogenin pretreatment normalized GSH levels and significantly reduced lipid peroxidation and nitrite levels in the stomach, as evaluated by the ethanol-induced gastric lesion model. The drug alone increased COX-2 expression and this effect was further enhanced in the presence of ethanol. It also decreased MPO release and significantly protected the gastric mucosa. In conclusion, we showed that hecogenin presents a significant gastroprotective effect that seems to be mediated by K⁺(ATP) channels opening and the COX-2/PG pathway. In addition, its antioxidant and anti-inflammatory properties may play a role in the gastroprotective drug effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.

PubMed

Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

2015-05-15

Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

PubMed Central

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga; Rezoagli, Emanuele; Thoonen, Robrecht; Cheng, Kai-Hung; Sosnovik, David E.; Scherrer-Crosbie, Marielle; Mootha, Vamsi K.; Zapol, Warren M.

2017-01-01

The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials. PMID:28483998

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome.

PubMed

Ferrari, Michele; Jain, Isha H; Goldberger, Olga; Rezoagli, Emanuele; Thoonen, Robrecht; Cheng, Kai-Hung; Sosnovik, David E; Scherrer-Crosbie, Marielle; Mootha, Vamsi K; Zapol, Warren M

2017-05-23

The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.

Multifocal bilateral metatarsal tuberculosis: a rare presentation.

PubMed

Vijay, Vipul; Sud, Alok; Mehtani, Anil

2015-01-01

Tuberculosis, or phthisis (consumption) as it was popularly known in the Greek era, has been endemic in Southeast Asia and Sub-Saharan Africa; however, the human immunodeficiency virus epidemic has seen the re-emergence of this disease in the areas in which it was not very commonly reported. With this, the need for understanding and treatment of rare presentations of tuberculosis has become of paramount importance to achieve the World Health Organization millennium goal of a "reversal of incidence by 2015." Foot involvement has been reported in 0.1% to 0.3% of extrapulmonary cases. Multifocal lesions have an incidence of <10% in osteoarticular tuberculosis. Bilateral feet involvement in multifocal tuberculosis has not yet been reported in either children or adults in published studies. We report a case of tuberculosis with lesions in the bilateral metatarsals, the occurrence of which is very rare. The diagnosis was mainly histopathologic owing to the paucibacillary nature of the disease. Early identification and treatment with antitubercular drugs will normally result in a good cosmetic and functional result. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance

NASA Technical Reports Server (NTRS)

Rosenberg, M. J. F.; Kreutzberg, G. A.; Galvan-Garza, R. C.; Mulavara, A. P.; Reschke, M. F.

2017-01-01

Upon return from long-duration spaceflight, 100% of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. Stochastic resonance (SR) is "noise benefit": adding noise to a system might increase the information (examples to the left and above). Stochastic vestibular stimulation (SVS), or low levels of noise applied to the vestibular system, improves balance and locomotor performance (Goel et al. 2015, Mulavara et al. 2011, 2015). In hemi-lesioned rat models, Samoudi et al. 2012 found that SVS increased GABA release on the lesioned, but not the intact side. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008) and was seen to reverse MS symptoms in rats after unilateral labyrinthectomy (Magnusson et al. 2000). Thus, SVS could be used to promote GABA pathways to reduce MS and promote adaptability, eliminate the need for PMZ or other performance-inhibiting drugs.

Systemic calicivirus epidemic in captive exotic felids.

PubMed

Harrison, Tara M; Sikarskie, James; Kruger, John; Wise, Annabel; Mullaney, Thomas P; Kiupel, Matti; Maes, Roger K

2007-06-01

A 5-day-old, mother-raised, Amur tiger cub (Panthera tigris altaica) presented with tongue ulcerations. Identical lesions appeared and progressed to sloughing of the tongue in the three littermates of this cub the following day. The lesions progressed in all cubs to include sloughing of the carpal, tarsal, metacarpal, and metatarsal foot pad epithelium. Oral ulcerations were also noted in adult African lions (Panthera leo) and Amur tigers (Panthera tigris altaica), but not in two adult snow leopards (Panthera uncia) housed in the same building. All adult cats had been previously vaccinated for common feline diseases including feline calicivirus (FCV). Detection of FCV RNA in oral secretions by a real-time reverse transcription polymerase chain reaction assay (RRT-PCR) confirmed FCV infection in the tiger cubs and one lion. A male lion and a male tiger cub died during the disease outbreak. RRT-PCR confirmed FCV in multiple tissues in both of these animals. A stray cat live-trapped outside the feline building during the epidemic was found to be positive for FCV by virus isolation and was thought to be the source of infection.

Expression of neuropeptides and their degrading enzymes in ACD.

PubMed

Bak, H; Lee, W J; Lee, Y W; Chang, S-E; Choi, J-H; Kim, M N; Kim, B J; Choi, Y S; Suh, H S

2010-04-01

Sensory neuropeptides such as neurokinin A or substance P modulate skin and immune cells the functions of neurokinin receptor activation during neurogenic inflammation. Zinc metalloproteases, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), effectively control the bioavailability of these neuropeptide mediators, which are released from sensory nerves, immune and skin cells during cutaneous responses to endogenous or exogenous noxious stimuli. Recently, studies have suggested that neuropeptides are one of the major pathogenetic fact in many dermatoses, such as allergic contact dermatitis (ACD), atopic dermatitis and psoriasis. To investigate the expression of major neuropeptides, SP and its degrading enzymes such as NEP and ACE, in the lesions of ACD. A skin biopsy was obtained from 10 patients with ACD. We analysed the expression of these molecules by immunohistochemical staining, confocal laser scanning microscopy, western blotting and reverse transcription PCR. There was a significant increase in expression of SP in keratinocytes from ACD lesions compared with those in control skin. There was also increased expression of ACE but not NEP in ACD. Neuropeptides and their degrading enzymes, particularly SP and ACE, have a significant role in the pathogenesis of ACD.

Encoding in the visual word form area: an fMRI adaptation study of words versus handwriting.

PubMed

Barton, Jason J S; Fox, Christopher J; Sekunova, Alla; Iaria, Giuseppe

2010-08-01

Written texts are not just words but complex multidimensional stimuli, including aspects such as case, font, and handwriting style, for example. Neuropsychological reports suggest that left fusiform lesions can impair the reading of text for word (lexical) content, being associated with alexia, whereas right-sided lesions may impair handwriting recognition. We used fMRI adaptation in 13 healthy participants to determine if repetition-suppression occurred for words but not handwriting in the left visual word form area (VWFA) and the reverse in the right fusiform gyrus. Contrary to these expectations, we found adaptation for handwriting but not for words in both the left VWFA and the right VWFA homologue. A trend to adaptation for words but not handwriting was seen only in the left middle temporal gyrus. An analysis of anterior and posterior subdivisions of the left VWFA also failed to show any adaptation for words. We conclude that the right and the left fusiform gyri show similar patterns of adaptation for handwriting, consistent with a predominantly perceptual contribution to text processing.

Comparison of Cochlear Cell Death Caused by Cisplatin, Alone and in Combination with Furosemide

PubMed Central

Xia, Li; Chen, Zhengnong; Su, Kaiming; Yin, Shankai; Wang, Jian

2014-01-01

Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis. PMID:23548607

Base excision repair, the redox environment and therapeutic implications.

PubMed

Storr, S J; Woolston, C M; Martin, S G

2012-01-01

Control of redox homeostasis is crucial for a number of cellular processes with deregulation leading to a number of serious consequences including oxidative damage such induction of DNA base lesions. The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. Pharmacological inhibition of BER is becoming an increasingly active area of research with the emergence of PARP inhibitors in cancer therapy. The redox status of the cell is modulated by a number of systems, including a large number of anti-oxidant enzymes who function in the control of superoxide and hydrogen peroxide, and ultimately in the release of the damaging hydroxyl radical. Here we provide an overview of reactive oxygen species (ROS) production and its modulation by antioxidant enzymes. The review also discusses the effect of ROS on the BER pathway, particularly in relation to cancer. Finally, as the modulation of the redox environment is of interest in cancer therapy, with certain agents having the potential to reverse chemo- and radiotherapy resistance or treat therapy related toxicity, we discuss redox modulating agents currently under development.

A quantitative real-time RT-PCR assay to measure TGF-beta mRNA and its correlation with hematologic, plasma chemistry and organo-somatic indices responses in triamcinolone-treated Atlantic menhaden, Brevoortia tyrannus.

PubMed

Johnson, A K; Harms, C A; Levine, J F; Law, J McHugh

2006-01-01

A quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assay was developed to measure transforming growth factor-beta (TGF-beta) in Atlantic menhaden (Brevoortia tyrannus), an estuarine-dependent species plagued by ulcerative skin lesions in the estuaries along the eastern United States. Atlantic menhaden were acclimated in a closed system for two weeks prior to initiation of the study. The synthetic glucocorticoid, triamcinolone acetonide (10mg/kg body weight) was administered by intracoelomic injection and its effect on the splenic mononuclear cell TGF-beta mRNA transcription, liver-somatic index, spleno-somatic index, hematology, and plasma chemistry were compared to untreated fish at 48 and 96h post-treatment. Triamcinolone-treated Atlantic menhaden showed suppression of TGF-beta mRNA production, neutrophilia, monocytosis, lymphopenia, and an increase in blood glucose concentrations. The health indices used in this study may help us interpret some of the changes observed during the development of ulcerative skin lesions in wild-caught menhaden.

Effect of micro lesions of the basal ganglia on ballistic movements in patients with deep brain stimulation.

PubMed

Singh, Arun; Mehrkens, Jan H; Bötzel, Kai

2012-03-15

Bradykinesia and hypokinesia are the prominent symptoms of substantia nigra degeneration in Parkinson's disease (PD). In segmental dystonia, movements of not affected limbs are not impaired. Here we studied the impact of the mere implantation of stimulation electrodes on the performance of fast movements in these two groups. We investigated 9 PD patients with subthalamic electrodes and 9 patients with segmental dystonia with electrodes in the globus pallidus internum. Patients were studied on the first postoperative day without electrical stimulation of the electrodes. Subjects had to perform boxing movements with either touching the target or stopping the fist in front of the target. PD subjects performed significantly faster movements in the touch-task only as compared to dystonic patients. No difference was seen in the stopping task. In conclusion, our findings suggest that a small subthalamic lesion in individuals with PD specifically reverses bradykinesia during simple ballistic movements (touch) but not during complex ones requiring more pre-programming (no-touch paradigm). Copyright © 2011 Elsevier B.V. All rights reserved.

Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant/vitamin food fortification in fathers

PubMed Central

McPherson, Nicole O.; Fullston, Tod; Kang, Wan Xian; Sandeman, Lauren Y.; Corbett, Mark A.; Owens, Julie A.; Lane, Michelle

2016-01-01

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health. PMID:27255552

Simulations of blood flow through a stenosed carotid artery

NASA Astrophysics Data System (ADS)

Lundin, Staffan; Meder, Samuel; Metcalfe, Ralph

2000-11-01

The human carotid artery is often the site of the formation of atherosclerotic lesions that can lead to severe reduction of blood flow to the brain, frequently resulting in a stroke. There is strong evidence that hemodynamic variables such as the wall shear stress and its spatial and temporal derivatives play a role in fostering atherosclerosis. To investigate the potential of these effects, we have performed unsteady, three-dimensional numerical simulations of blood flow through the carotid bifurcation in the presence of stenoses of varying degrees and eccentricities. The simulations indicate that regions of low maximum and minimum shear stress correlate better with lesion prone sites than low average wall shear stress. As the degree of stenosis increases, it is found that the downstream flow changes drastically for stenoses greater than about 25Downstream eddies are generated during systole that create local shear stress peaks on the internal carotid artery wall, resulting in significant reduction in flow rates through the internal carotid artery. Large secondary flows develop, and there are also periods of flow reversal during the systolic/diastolic cycle.

Hirschsprung's disease in twin to twin transfusion syndrome: a case report.

PubMed

Park, Hye Won; Cho, Min Jeng; Kim, Wook Youn; Kwak, Byung Ok; Kim, Min Hee

2014-12-14

Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period. In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases. We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray. The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio. A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon.

Approach to the patient with Parkinson disease.

PubMed

Johnson, Kevin E

2015-06-01

Parkinson disease (PD) is a progressive neurodegenerative disease with motor, nonmotor, and behavioral findings. Imaging technology advances have allowed the characterization of the underlying pathologic changes to the brain and identification of specific lesions in dopaminergic neurons. Although certain imaging techniques allow for detection up to 20 years before the onset of motor symptoms, these advances have yet to produce meaningful treatments to halt the disease or reverse its course. Current treatments are directed at optimizing symptomatic management. Referral to a movement disorder specialist familiar with PD should be considered for providers with limited familiarity in diagnosis or treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Thallium-201 scintigraphy in the diagnosis and management of myocardial sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fields, C.L.; Ossorio, M.A.; Roy, T.M.

1990-03-01

We have described three patients with clinical evidence of myocardial sarcoidosis to illustrate the utility of thallium-201 scintigraphy in demonstrating the myocardial lesions. Both the symptomatic and asymptomatic individuals studied showed the characteristic reverse redistribution phenomenon. No abnormalities were seen during the exercise phase of the thallium study, but myocardial defects were detected in each patient when repeat studies were obtained at rest six hours later. Steroid therapy resolved the defects in each case. We propose thallium-201 scintigraphy of the heart as a safe and useful tool for documenting myocardial involvement in sarcoidosis and following the effects of therapy.

A role for synaptic and network plasticity in controlling epileptiform activity in CA1 in the kainic acid-lesioned rat hippocampus in vitro.

PubMed Central

Bernard, C; Wheal, H V

1996-01-01

1. Stimulation of the surviving afferents in the stratum radiatum of the CA1 area in kainic acid-lesioned hippocampal slices produced graded epileptiform activity, part of which (> 20%) involved the activation of N-methyl-D-aspartate (NMDA) receptors. There was also a failure of synaptic inhibition in this region. In this preparation, we have tested the effects of low-frequency stimulation (LFS; 1 Hz for 15 min) on synaptic responses and epileptiform activity. 2. LFS resulted in long-term depression (LTD) of excitatory synaptic potentials (EPSPs), long-term decrease of population spike amplitudes (PSAs) and EPSP-spike (E-S) potentiation. Evoked epileptiform activity was reduced but neurons had a higher probability of discharge. LTD could be reversed by subsequent tetanic stimulation whereas E-S dissociation remained unchanged. Synaptic and network responses could be saturated towards either potentiation or depression. However, E-S potentiation was maximal following the first conditioning stimulus. 3. NMDA receptor-mediated responses were pharmacologically isolated. LFS resulted in LTD of synaptic responses, long-term decrease of PSAs and E-S depression. These depressions could not be reversed by subsequent tetanic stimulation. alpha-Amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and NMDA receptor-mediated responses were then measured in isolation before and following conditioning stimuli. LFS was shown to simultaneously produce LTD of AMPA and NMDA receptor-mediated responses. E-S potentiation of the AMPA component and E-S depression of the NMDA component occurred coincidentally. 4. LTD of AMPA and NMDA receptor-mediated responses were shown to be NMDA dependent. In contrast, E-S potentiation and depression occurred even when NMDA receptors were pharmacologically blocked. 5. These findings indicate that synaptic responses could be modified bidirectionally in the CA1 area of kainic acid-lesioned rat hippocampus in an NMDA receptor-dependent manner. However, E-S dissociations were independent of the activation of NMDA receptors, hinting at mechanisms different from those of synaptic LTD. We suggest that changes in E-S coupling were caused by a modification of the firing threshold of the CA1 pyramidal neurons. Furthermore, the firing mechanisms controlling NMDA and AMPA receptor-mediated network activity appeared to be different. The possible use of LFS applied to the hippocampus as a clinical intervention to suppress epileptiform activity is discussed. PMID:8866357

Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma

PubMed Central

Ryu, Ji Kon; Matthaei, Hanno; dal Molin, Marco; Hong, Seung-Mo; Canto, Marcia I.; Schulick, Richard D.; Wolfgang, Christopher; Goggins, Michael G.; Hruban, Ralph H.; Cope, Leslie; Maitra, Anirban

2011-01-01

Background Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer. Methods Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The ‘mucinous’ cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the ‘nonmucinous’ cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas. Results Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%. Conclusion This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas. PMID:21757972

The Alzheimer Pandemic: Is Paracetamol to Blame?

PubMed Central

Jones, Günther Robert Norman

2013-01-01

Historical Background: The clinical recognition of a form of dementia closely resembling Alzheimer's disease dates from around 1800. The role of analgesics derived from coal-tar in the spread of the pandemic is traced in terms of the introduction of phenacetin (PN) in 1887; its nephrotoxicity; the observation of lesions characteristic of the disease by Fischer and Alzheimer; the discovery of paracetamol (PA) as the major metabolite of PN; the linking of kidney injury and dementia with high PN usage; and the failure of PN replacement by PA to halt and reverse the exponential, inexorable rise in the incidence of Alzheimer-type dementia. Fischer observed his first case before Alzheimer; it is proposed to rename the syndrome Fischer-Alzheimer disease (F-AD). Disease development: PA-metabolising enzymes are localised in the synaptic areas of the frontal cortex and hippocampus, where F-AD lesions arise. The initiating chemical lesions in liver poisoning comprise covalent binding of a highly reactive product of PA metabolism to proteins; similar events are believed to occur in brain, where alterations in the antigenic profiles of cerebral proteins activate the microglia. β-Amyloid forms, and, like PA itself, induces nitric oxide synthase. Peroxynitrite modifies cerebral proteins by nitrating tyrosine residues, further challenging the microglia and exacerbating the amyloid cascade. Spontaneous reinnervation, N-acetyl cysteine administration and tyrosine supplementation may attenuate the early stages of F-AD development. Conclusion: F-AD is primarily a man-made condition with PA as its principal risk factor. PMID:24350947

Molecular effects of doxycycline treatment on pterygium as revealed by massive transcriptome sequencing.

PubMed

Larráyoz, Ignacio M; de Luis, Alberto; Rúa, Oscar; Velilla, Sara; Cabello, Juan; Martínez, Alfredo

2012-01-01

Pterygium is a lesion of the eye surface which involves cell proliferation, migration, angiogenesis, fibrosis, and extracellular matrix remodelling. Surgery is the only approved method to treat this disorder, but high recurrence rates are common. Recently, it has been shown in a mouse model that treatment with doxycycline resulted in reduction of the pterygium lesions. Here we study the mechanism(s) of action by which doxycycline achieves these results, using massive sequencing techniques. Surgically removed pterygia from 10 consecutive patients were set in short term culture and exposed to 0 (control), 50, 200, and 500 µg/ml doxycycline for 24 h, their mRNA was purified, reverse transcribed and sequenced through Illumina's massive sequencing protocols. Acquired data were subjected to quantile normalization and analyzed using cytoscape plugin software to explore the pathways involved. False discovery rate (FDR) methods were used to identify 332 genes which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. A high correlation was obtained when comparing ultrasequencing data with qRT-PCR and ELISA results. Doxycycline significantly modified the expression of important cellular pathways in pterygium cells, in a way which is consistent with the observed efficacy of this antibiotic to reduce pterygium lesions in a mouse model. Clinical trials are under way to demonstrate whether there is a benefit for human patients.

Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

NASA Astrophysics Data System (ADS)

Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

2015-07-01

Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001 n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.

Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions.

PubMed

Price, C J; Warburton, E A; Moore, C J; Frackowiak, R S; Friston, K J

2001-05-15

Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.

Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures.

PubMed

Howe, Charles L; Kaptzan, Tatiana; Magaña, Setty M; Ayers-Ringler, Jennifer R; LaFrance-Corey, Reghann G; Lucchinetti, Claudia F

2014-05-01

Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sjögren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development. Copyright © 2014 Wiley Periodicals, Inc.

Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

PubMed

Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

2007-11-01

Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

The frequency of perceived stress, anxiety, and depression in patients with common pathologies affecting voice.

PubMed

Dietrich, Maria; Verdolini Abbott, Katherine; Gartner-Schmidt, Jackie; Rosen, Clark A

2008-07-01

The study's objectives were to investigate (1) the frequency of perceived stress, anxiety, and depression for patients with common voice disorders, (2) the distribution of these variables by diagnosis, and (3) the distribution of the variables by gender. Retrospective data were derived from self-report questionnaires assessing recent stress (Perceived Stress Scale-10), anxiety, and depression (Hospital Anxiety and Depression Scale) in a cohort of new patients presenting to a voice clinic. Data are presented on 160 patients with muscle tension dysphonia (MTD), benign vocal fold lesions, paradoxical vocal fold movement disorder (PVFMD), or glottal insufficiency. Pooled data indicated that average stress, anxiety, and depression scores were similar to those found for the healthy population. However, 25.0%, 36.9%, and 31.2% of patients showed elevated stress, anxiety, and depression scores, respectively, compared to norms. Patients with PVFMD had the most frequent occurrence-and patients with glottal insufficiency had the least frequent occurrence of elevated stress, anxiety, and depression. Stress and depression were more common with MTD than with lesions, whereas reverse results were obtained for anxiety. More females than males had elevated stress, anxiety, and depression scores. The data are consistent with suggestions that stress, anxiety, and depression may be common among some patients with PVFMD, MTD, and vocal fold lesions and more common for women than men. However, individual variability in the data set was large. Further studies should evaluate the specific role of these conditions for selected categories of voice disorders in susceptible individuals.

Multi-parametric monitoring of high intensity focused ultrasound (HIFU) treatment using harmonic motion imaging for focused ultrasound (HMIFU)

NASA Astrophysics Data System (ADS)

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa

2012-11-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and relative phase-shift during high energy HIFU where tissue boiling occurs. Forty three (n=18) thermal lesions were formed in ex vivo canine liver specimens. Two dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10-, 20-and 30-s HIFU durations at three different acoustic powers of 8, 10, and 11W. For the 10-, 20-, and 30-s treatment cases, a steady decrease in the displacement (-8.67±4.80, -14.44±7.77, 24.03±12.11μm), compressive strain -0.16±0.06, -0.71±0.30, -0.68±0.36 %, and phase shift +1.80±6.80, -15.80±9.44, -18.62±13.14 ° were obtained, respectively, indicating overall increase of relative stiffness and decrease of the viscosity-to-stiffness ratio during heating. After treatment, 2D HMI displacement images of the thermal lesions showed an increased lesion-to-background contrast of 1.34±0.19, 1.98±0.30, 2.26±0.80 and lesion size of 40.95±8.06, 47.6±4.87, and 52.23±2.19 mm2, respectively, which was validated again with pathology 25.17±6.99, 42.17±1.77, 47.17±3.10 mm2. Additionally, studies also investigated the performance of mutli-parametric monitoring under the influence of boiling and attenuation change due to tissue boiling, where discrepancies were found such as deteriorated displacement SNR and reversed lesion-to-background displacement contrast with indication on possible increase in attenuation and tissue gelatification or pulverization. Despite the challenge of the boiling mechanism, the relative phase shift served as consist biomechanical tissue response independent of changes in acoustic properties throughout the HIFU treatment. In addition, the 2D HMI displacement images were able to confirm and quantify the change in dimensions of the thermal lesion site. Therefore, the multi-parametric HMIFU was shown capable of monitoring and mapping tissue viscoelastic response changes during and after HIFU treatment.

Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation.

PubMed

Stehling, Michael K; Guenther, Enric; Mikus, Paul; Klein, Nina; Rubinsky, Liel; Rubinsky, Boris

2016-01-01

Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation.

Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation

PubMed Central

Mikus, Paul; Klein, Nina; Rubinsky, Liel; Rubinsky, Boris

2016-01-01

Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs “Synergistic electrolysis and electroporation” (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation. PMID:26866693

Posterior Reversible Leukoencephalopathy Syndrome: Case Series and Review of the Literature.

PubMed

Pirola, Juan Pablo; Baenas, Diego Federico; Haye Salinas, María Jezabel; Benzaquén, Nadia Raquel; Colazo, Marcela; Borghi, María Victoria; Lucero, Cecilia; Álvarez, Ana Cecilia; Retamozo, Soledad; Alvarellos, Alejandro; Saurit, Verónica; Caeiro, Francisco

2018-05-30

To describe clinical manifestations, antecedents, comorbidities and associated treatments, imaging findings, and follow-up in patients with posterior reversible encephalopathy syndrome. A retrospective, descriptive analysis of admitted patients was performed between June 2009 and May 2014 in a third-level care hospital. We evaluated age, sex, comorbidities, symptoms, values of blood pressure at admission, renal function, medication and time elapsed until the disappearance of symptoms. Thirteen patients were included. In all, 77% of them had a history of hypertension at baseline and 85% had impaired renal function. The most prevalent comorbidity was renal transplantation, and 85% had deterioration of renal function. Five of the patients had undergone renal transplantation. The most common clinical manifestation was seizures. All had subcortical lesions and bilateral parietooccipital involvement was the finding most frequently observed. This syndrome should be taken into account in the differential diagnoses of patients presenting with acute neurological syndromes and the abovementioned risk factors. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions

PubMed Central

Dubey, Jitender P.; Ferreira, Leandra R.; Alsaad, Mohammad; Verma, Shiv K.; Alves, Derron A.; Holland, Gary N.; McConkey, Glenn A.

2016-01-01

Background The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Methodology/Principal Findings Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. Conclusion/Significance This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations. PMID:27228262

Measuring discrimination- and reversal learning in mouse models within 4 days and without prior food deprivation

PubMed Central

Smit, August B.; Verhage, Matthijs

2016-01-01

Many neurological and psychiatric disorders are characterized by deficits in cognitive flexibility. Modeling cognitive flexibility in mice enables the investigation of mechanisms underlying these deficits. The majority of currently available behavioral tests targeting this cognitive domain are reversal learning tasks that require scheduled food restriction, extended training periods and labor-intensive, and stress-inducing animal handling. Here, we describe a novel 4-day (4-d) continuously running task measuring discrimination- and reversal learning in an automated home cage (CognitionWall DL/RL task) that largely eliminates these limitations. In this task, mice can earn unlimited number of food rewards by passing through the correct hole of the three-holed CognitionWall. To assess the validity and sensitivity of this novel task, the performance of C57BL/6J mice, amyloid precursor protein/presenilin1 transgenic (APP/PS1) mice, α-calmodulin kinase-II (αCaMKII) T305D knock-in mice, and mice with an orbitofrontal cortex lesion were examined. We found that C57BL/6J mice reach stable performance levels within the 4 d of the task, while experiencing only slight reductions in weight and no major effects on circadian rhythm. The task detected learning deficits in APP/PS1 transgenic and αCaMKII T305D mutant mice. Additionally, we established that the orbitofrontal cortex underlies reversal learning performance in our task. Because of its short duration and the absence of food deprivation and concurrent weight loss, this novel automated home-cage task substantially improves comprehensive preclinical assessment of cognitive functions in mouse models of psychiatric and neurological disorders and also enables analysis during specific developmental stages. PMID:27918287

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga

The most common pediatric mitochondrial disease is Leigh syn-drome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that contin-uously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated sur-vival curves and organ pathology in Ndufs4 KO mice exposed to hypoxiamore » or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as contin-uous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy re-verses their established neurological disease, evidenced by im-proved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hyp-oxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.« less

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

DOE PAGES

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga; ...

2017-05-08

The most common pediatric mitochondrial disease is Leigh syn-drome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that contin-uously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated sur-vival curves and organ pathology in Ndufs4 KO mice exposed to hypoxiamore » or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as contin-uous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy re-verses their established neurological disease, evidenced by im-proved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hyp-oxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.« less

Measuring discrimination- and reversal learning in mouse models within 4 days and without prior food deprivation.

PubMed

Remmelink, Esther; Smit, August B; Verhage, Matthijs; Loos, Maarten

2016-11-01

Many neurological and psychiatric disorders are characterized by deficits in cognitive flexibility. Modeling cognitive flexibility in mice enables the investigation of mechanisms underlying these deficits. The majority of currently available behavioral tests targeting this cognitive domain are reversal learning tasks that require scheduled food restriction, extended training periods and labor-intensive, and stress-inducing animal handling. Here, we describe a novel 4-day (4-d) continuously running task measuring discrimination- and reversal learning in an automated home cage (CognitionWall DL/RL task) that largely eliminates these limitations. In this task, mice can earn unlimited number of food rewards by passing through the correct hole of the three-holed CognitionWall. To assess the validity and sensitivity of this novel task, the performance of C57BL/6J mice, amyloid precursor protein/presenilin1 transgenic (APP/PS1) mice, α-calmodulin kinase-II (αCaMKII) T305D knock-in mice, and mice with an orbitofrontal cortex lesion were examined. We found that C57BL/6J mice reach stable performance levels within the 4 d of the task, while experiencing only slight reductions in weight and no major effects on circadian rhythm. The task detected learning deficits in APP/PS1 transgenic and αCaMKII T305D mutant mice. Additionally, we established that the orbitofrontal cortex underlies reversal learning performance in our task. Because of its short duration and the absence of food deprivation and concurrent weight loss, this novel automated home-cage task substantially improves comprehensive preclinical assessment of cognitive functions in mouse models of psychiatric and neurological disorders and also enables analysis during specific developmental stages. © 2016 Remmelink et al.; Published by Cold Spring Harbor Laboratory Press.

Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain

PubMed Central

2013-01-01

Background We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). Methods We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. Results We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). Conclusion The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058. PMID:24325764

Rapid compensatory changes in GABA receptor efficacy in rat vestibular neurones after unilateral labyrinthectomy

PubMed Central

Yamanaka, Toshiaki; Him, Aydin; Cameron, Susan A; Dutia, Mayank B

2000-01-01

The inhibitory effects of the GABAA agonist muscimol and the GABAB agonist baclofen on tonically active medial vestibular nucleus (MVN) neurones were recorded in slices of the rat dorsal brainstem in vitro, to determine whether any changes occurred in the functional efficacy of GABAergic inhibition in these cells during the initial rapid stage of ‘vestibular compensation’, the behavioural recovery that takes place after unilateral labyrinthectomy (UL). These experiments were carried out in preparations where the midline was cut, severing all commissural connections between the two vestibular nuclei. Slices of the MVN were prepared from normal animals and animals that had been unilaterally labyrinthectomised 4 h earlier. The mean in vitro discharge rate of MVN neurones in the rostral region of the ipsi-lesional nucleus after UL was significantly higher than that in control slices, confirming our earlier reports of an increase in intrinsic excitability of these cells in the early stage of vestibular compensation. The in vitro discharge rates of caudal ipsi-lesional MVN cells, and rostral and caudal contra-lesional MVN cells, were not different from controls. Muscimol and baclofen caused reversible, dose-related inhibition of the tonic discharge rate of MVN cells in control slices. In slices prepared from UL animals, MVN cells in the rostral region of the ipsi-lesional nucleus showed a marked downregulation of their response to both muscimol and baclofen, seen as a rightward shift and a decrease in slope of the dose-response relationships for the two agonists. In the contra-lesional nucleus, there was a small but significant upregulation of the responsiveness of both rostral and caudal MVN cells to baclofen, and a marked upregulation of the responsiveness of caudal MVN cells to muscimol. In slices from animals that had undergone bilateral labyrinthectomy 4 h earlier, the downregulation of the functional efficacy of GABA receptors in the rostral MVN cells did not occur. The changes in GABA receptor efficacy after UL are therefore not due to the vestibular de-afferentation itself, but are instead due to the imbalance in excitability of the vestibular nuclei of the lesioned and intact sides, and the enhanced commissural inhibition of the ipsi-lesional MVN cells that follows UL. The downregulation of GABA receptor efficacy in the ipsi-lesional MVN neurones is functionally compensatory, in that their response to commissural and cerebellar inhibitory drive will be significantly reduced after UL. Their intrinsic membrane conductances, and their remaining excitatory synaptic inputs, will consequently be more effective in causing depolarisation and the restoration of resting activity. Simultaneously the upregulation of GABAergic efficacy in the contra-lesional MVN will tend to reduce the hyperactivity on the contralateral side. These adaptive changes therefore represent a plausible cellular mechanism for the recovery of resting discharge in the ipsi-lesional MVN neurones, and the ‘re-balancing’ of the excitability of the vestibular neurones of the lesioned and intact sides, as occurs after UL in vivo. We propose that the adaptive regulation of the functional efficacy of GABA receptors in the MVN neurones may be an important cellular mechanism for the ‘homeostasis of bilateral excitability’ of the vestibular nuclei of the two sides. PMID:10699085

Understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy.

PubMed

Nery, José Augusto da Costa; Bernardes Filho, Fred; Quintanilha, Juliana; Machado, Alice Miranda; Oliveira, Soraya de Souza Chantre; Sales, Anna Maria

2013-01-01

A type 1 reaction or reversal reaction is expressed clinically by inflammatory exacerbation of the skin lesions and nerve trunks, consequently leading to sensory and motor alterations. It occurs in non-polar forms of leprosy, although it can occur in a small percentage of sub-polar LL treated patients. Disabilities, deformities and morbidity, still present in leprosy, are mainly caused by these acute episodes. The recognition of reactional states is imperative for an early approach and efficient management, to avoid the emergence of disabilities that stigmatize the disease. This review aims to describe the clinical aspects, immunopathogenesis, epidemiology, histopathological features and therapeutics of type 1 reactions.

Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

PubMed

Ishii, Kiyoko; Komaki, Hirofumi; Ohkuma, Aya; Nishino, Ichizo; Nonaka, Ikuya; Sasaki, Masayuki

2010-09-01

We report an adolescent case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by intermittent nausea and depressive state as early symptoms. At the age of 12 years and 11 months, the patient experienced intermittent nausea and vomiting, and depressive state. She was on medication for depression for 5 months but it was ineffective. Brain magnetic resonance imaging showed disseminated high-intensity areas in the periventricular white matter and in the splenium of the corpus callosum on T2-weighted images and fluid-attenuated inversion-recovery images. Progressive muscle weakness occurred and blood creatine kinase level was found to be elevated. The muscle biopsy revealed lipid storage myopathy. Urine organic acid analysis and mutation analysis of the ETFDH gene confirmed the diagnosis of MADD. With oral supplements of riboflavin and l-carnitine, in addition to a high-calorie and reduced-fat diet, her clinical symptoms improved dramatically. Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. Copyright 2009 Elsevier B.V. All rights reserved.

Age-related white matter integrity differences in oldest-old without dementia.

PubMed

Bennett, Ilana J; Greenia, Dana E; Maillard, Pauline; Sajjadi, S Ahmad; DeCarli, Charles; Corrada, Maria M; Kawas, Claudia H

2017-08-01

Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life. Copyright © 2017 Elsevier Inc. All rights reserved.